| 1. |
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| 2. |
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| 3. |
- Rueenauver, K., et al.
(författare)
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Prognostic significance of YWHAZ expression in localized prostate cancer
- 2014
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 17:4, s. 310-314
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate cancer (PCa) patients are often over-treated because of the lack of biomarkers needed to distinguish the lethal from the indolent form of PCa. YWHAZ was recently identified as a potential therapeutic target in castration-resistant PCa (CRPC). Therefore, this study focused on determining the prognostic significance of YWHAZ in localized PCa.METHODS: YWHAZ expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded tissue from 213 men who underwent radical prostatectomy. Kaplan-Meier analysis and Cox proportional-hazards models were, used to assess the prognostic value of YWHAZ intensity.RESULTS: High YWHAZ expression was strongly associated with high Gleason score at the time of diagnosis (P<0.001) and PSA relapse (P=0.001). Importantly, patients with high expression of YWHAZ had a higher risk of CRPC development (P=0.002) and reduced survival time (P=0.002).CONCLUSIONS: Our findings indicate that YWHAZ could serve as a promising prognostic biomarker in localized PCa to predict poor prognosis and to identify a subgroup of tumors, which might benefit from earlier adjuvant or YWHAZ-targeted therapy.
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| 4. |
- Vikerfors, Anders, 1984-, et al.
(författare)
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Plasma Levels of Pentraxin 3 : A Potential Prognostic Biomarker in Urinary Bladder Cancer Patients
- 2024
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 25:6
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Tidskriftsartikel (refereegranskat)abstract
- Urinary bladder cancer (BC) represents a major health issue, and identifying novel biomarkers for early disease detection and outcome prediction is paramount. It has already been established that the immune system plays a role in tumour initiation and progression in which the inflammatory marker pentraxin 3 (PTX3) might be involved, presenting a variety of functions in different cancers. The aim of this study was to investigate whether plasma levels of PTX3 could be used as a biomarker for patients with BC. Plasma levels of PTX3 were determined in 118 BC patients and 50 controls by ELISA. Patients with BC had significantly higher PTX3 levels compared to controls. The value as a diagnostic biomarker is probably limited, however, since no significant difference in PTX3 levels was seen between patients with non-muscle-invasive BC and controls; they were seen only between patients with muscle-invasive disease and controls. However, the potential value of PTX3 as a prognostic biomarker was indicated by significantly higher PTX3 levels in patients who developed metastatic disease during follow-up compared to patients who did not develop metastatic disease. The conclusions from this study are that plasma levels of PTX3 have limited value as a diagnostic biomarker, although they have potential as a prognostic biomarker for patients with BC.
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| 5. |
- Vikerfors, Anders, 1984-, et al.
(författare)
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Soluble PD-L1 in Serum and Urine in Urinary Bladder Cancer Patients
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:22
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Tidskriftsartikel (refereegranskat)abstract
- Soluble PD-L1 (sPD-L1) levels have been identified as a potential biomarker for various cancers, but its diagnostic and prognostic value in urinary bladder cancer (BC) remains to be fully elucidated. In this study, we investigated sPD-L1 levels in serum and urine samples from 132 patients with BC and compared them to 51 patients with hematuria (controls). The levels of sPD-L1 in serum and urine were determined using ELISA. Soluble PD-L1 could be detected in 99.5% of the serum samples and 34.4% of the urine samples. Patients diagnosed with BC had significantly higher urinary levels of sPD-L1, compared to controls, however no difference were found in serum sPD-L1 levels (p = 0.038 and p = 0.61, respectively). Significantly higher serum sPD-L1 levels were found in patients with muscle invasive disease and metastatic disease, compared to patients with non-muscle invasive BC and non-metastatic disease (p < 0.05). There was also a trend for higher urine sPD-L1 levels in patients with metastatic disease, compared to patients with non-metastatic disease (p = 0.05). The results from this study suggest that sPD-L1 in serum, but not in urine, could be a potential prognostic biomarker for patients with BC.
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| 6. |
- Brady, Lauren, et al.
(författare)
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Correlation of integrated ERG/PTEN assessment with biochemical recurrence in prostate cancer
- 2021
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Ingår i: Cancer Treatment and Research Communications. - : Elsevier. - 2468-2942. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Prostate cancer is a heterogeneous disease, with a complex molecular landscape that evolves throughout disease progression. Common alterations in genes such as ERG and PTEN have been attributed to worse prognosis. This study aimed to further examine the clinical relevance of PTEN and ERG expression in a cohort of patients with prostate cancer post radical prostatectomy.METHODS: Tissue microarrays were constructed from 132 patients with prostate cancer from the Irish Prostate Cancer Research Consortium and University Hospital of Orebro, Sweden. Patients were divided into three groups - Group 1: biochemical recurrence, Group 2: no biochemical recurrence and Group 3: immediate progression after surgery. PTEN and ERG immunohistochemical analysis was performed and the association between expression levels and clinical parameters were compared.RESULTS: Pathological stage pT3 tumours were more common at borderline significantly higher levels amongst patients who biochemically recurred when compared to patients who did not recur after radical prostatectomy (p = 0.05). ERG and PTEN expression levels were compared separately and concurrently across all three patient groups. Lack of ERG expression was strongly associated with immediate progression after surgery (p = 0.029). Loss of/low PTEN trended towards an association with immediate progression, however this was not statistically significant (p = 0.066).CONCLUSION: In this study, negative ERG expression was strongly associated with immediate biochemical progression after radical prostatectomy. Moreover, a trend towards a relationship between aberrant PTEN expression and progression was observed. Additional studies with long-term follow up data may provide further clinical insight into the genomic heterogeneity in this population.
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| 7. |
- Braegelmann, Johannes, et al.
(författare)
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Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer
- 2017
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research Inc.. - 1078-0432 .- 1557-3265. ; 23:7, s. 1829-1840
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches.Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities (n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer (n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq.Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancerwasmarked by high expression of CDK19. In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8were present inmetastases. In vitro, inhibition ofCDK19 and CDK8 by knockdown or treatment with a selective CDK8/ CDK19 inhibitor significantly decreased migration and invasion.Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer.
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| 8. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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A miRNA expression signature that separates between normal and malignant prostate tissues
- 2011
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Ingår i: Cancer Cell International. - : BioMed Central (BMC). - 1475-2867. ; :11, s. 14-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMicroRNAs (miRNAs) constitute a class of small non-coding RNAs that post-transcriptionally regulate genes involved in several key biological processes and thus are involved in various diseases, including cancer. In this study we aimed to identify a miRNA expression signature that could be used to separate between normal and malignant prostate tissues.ResultsNine miRNAs were found to be differentially expressed (p <0.00001). With the exception of two samples, this expression signature could be used to separate between the normal and malignant tissues. A cross-validation procedure confirmed the generality of this expression signature. We also identified 16 miRNAs that possibly could be used as a complement to current methods for grading of prostate tumor tissues.ConclusionsWe found an expression signature based on nine differentially expressed miRNAs that with high accuracy (85%) could classify the normal and malignant prostate tissues in patients from the Swedish Watchful Waiting cohort. The results show that there are significant differences in miRNA expression between normal and malignant prostate tissue, indicating that these small RNA molecules might be important in the biogenesis of prostate cancer and potentially useful for clinical diagnosis of the disease.
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| 9. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate
- 2013
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Ingår i: BMC Cancer. - London, United Kingdom : BioMed Central (BMC). - 1471-2407. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate. Methods: Patients with prostate cancer were included in the study if they had a tumor with Gleason grade 3 in the PZ, the TZ, or both (n=16). Normal prostate tissue was collected from men undergoing cystoprostatectomy (n=20). The expression of 667 unique miRNAs was investigated using TaqMan low density arrays for miRNAs. Student's t-test was used in order to identify differentially expressed miRNAs, followed by hierarchical clustering and principal component analysis (PCA) to study the separation of the tissues. The ADtree algorithm was used to identify markers for classification of tissues and a cross-validation procedure was used to test the generality of the identified miRNA-based classifiers. Results: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified. Conclusions: The results of this study indicate that the major differences in the transcription program are those arising during tumor development, rather than during normal tissue development. In addition, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the different zones. MicroRNA signatures that are specific for PZ and TZ tumors could also lead to more accurate prognoses, since tumors arising in the PZ tend to be more aggressive than tumors arising in the TZ.
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| 10. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ) and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation to the difference in propensity of tumors in the zones of the prostate.Methods:The expression of 667 unique miRNAs was investigated in normal and malignant transition zone and peripheral zone prostate tissues using TaqMan low density arrays for miRNAs. Student’s t-test was used in order to identify differentially expressed miRNAs and hierarchical clustering and principal component analyses were used to note the separation of the tissues. A cross-validation test using the ADtree algorithm was used to test the generality of the identified miRNA signatures.Results:The Student’s t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentiallyexpressed miRNAs between normal and malignant tissues showed a perfect separation between samples while analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmedt hese results and several potential miRNA markers were identified.Conclusions:The results of this study indicate that the major differences in the transcription programme are those arising during tumor development, rather than during normal tissue development. In conclusion, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ, indicating that the PZ are more prone to tumor development than the TZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the transition- or peripheral zone.
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| 11. |
- Carlsson, Jessica, 1984-
(författare)
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Identification of miRNA expression profiles for diagnosis and prognosis of prostate cancer
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer of the prostate (CaP) is the most common malignancy diagnosed in men in the Western society. During the last years, prostate specific antigen (PSA) has been used as a biomarker for CaP, although a high PSA value is not specific for CaP. Thus, there is an urgent need for new and improved diagnostic markers for CaP.In this thesis, the aim was to find a miRNA signature for diagnosis of CaP and to elucidate if differences in behavior between transition zone and peripheral zone tumors are reflected in miRNA expression. One of the major findings is anexpression signature based on nine miRNAs that with high accuracy (85%) could classify normal and malignant tissues from the transition zone of the prostate. The results furthermore show that the major differences in miRNA expression are found between normal and malignant tissues, rather than between the different zones. In addition, tumors arising in the peripheral zone have fewer changes in miRNA expression compared to tumors in the transition zone, indicating that the peripheral zone is more prone to tumor development compared to the transition zone of the prostate.A crucial step in pre-processing of expression data, in order to differentiate true biological changes, is the normalization step. Therefore, an additional aim of this thesis was to compare different normalization methods for qPCR array data in miRNA expression experiments. The results show that data-driven methods based on quantile normalization performs the best. The results also show that in smaller miRNA expression studies, only investigating a few miRNAs, RNU24 is the most suitable endogenous control gene for normalization.Taken together, the results in this thesis show the importance of miRNAs and the possibility of their future use as biomarkers in the field of prostate cancer.
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| 12. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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PD-L1 Expression is Associated With Poor Prognosis in Renal Cell Carcinoma
- 2020
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Ingår i: Applied immunohistochemistry & molecular morphology (Print). - : Lippincott Williams & Wilkins. - 1541-2016 .- 1533-4058. ; 28:3, s. 213-220
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Tidskriftsartikel (refereegranskat)abstract
- Programmed death ligand 1 (PD-L1) is a protein which, when interacting with its receptor programmed death 1, acts as a negative regulator of the antitumor T-cell-mediated immune response. The prognostic value of PD-L1 expression in renal cell carcinoma (RCC) has been controversial. In this study, the prognostic value of PD-L1 expression in RCC was evaluated by analyzing PD-L1 immunoreactivity in tumor cells and tumor-infiltrating immune cells (TIICs) in 346 RCC patients with long-term follow-up. PD-L1 positivity in tumor cells was associated with higher World Health Organization nucleolar grade (P<0.001), recurrence (P=0.011), and death due to RCC (P=0.031). PD-L1 positivity in TIICs was associated with higher nucleolar grade (P<0.001), higher T-stage (P=0.031), higher N-stage (P=0.01), recurrence (P=0.007), and death due to RCC (P=0.001). A significant positive association of time to cancer-specific death with both PD-L1-positive tumor cells and TIICs were also found. The data indicate that RCC patients with PD-L1-positive tumor cells and TIICs are at significant risk for cancer progression and the expression may be used as a complementary prognostic factor in the management of RCC patients.
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| 13. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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Prostate cancer and inflammation : The role of miRNAs
- 2013
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Ingår i: European Medical Journal Oncology. - United Kingdom : Gorely New Media Ltd.. - 2054-619X. ; , s. 56-60
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Forskningsöversikt (refereegranskat)abstract
- Approximately 15-20% of all human cancers are assumed to be a result of infection and chronic inflammation due to a constant supply of cytokines and reactive oxygen species, giving rise to genomic instability and a subsequent tumour development. In recent years, chronic inflammation has also been hypothesised to influence prostate carcinogenesis, since both acute and chronic inflammation is commonly seen in prostatic tissues. The signalling pathways involved in the immune response and tumour development are overlapping with each other, and it has been proposed that miRNAs are a possible link between the two processes. In this review, we are describing some of the miRNAs which could constitute a conceivable link between inflammation and prostate cancer.
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| 14. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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Quantity and quality of nucleic acids extracted from archival formalin fixed paraffin embedded prostate biopsies
- 2018
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Ingår i: BMC Medical Research Methodology. - : BioMed Central. - 1471-2288. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In Sweden, human tissue samples obtained from diagnostic and surgical procedures have for decades been routinely stored in a formalin-fixed, paraffin-embedded, form. Through linkage with nationwide registers, these samples are available for molecular studies to identify biomarkers predicting mortality even in slow-progressing prostate cancer. However, tissue fixation causes modifications of nucleic acids, making it challenging to extract high-quality nucleic acids from formalin fixated tissues.METHODS: In this study, the efficiency of five commercial nucleic acid extraction kits was compared on 30 prostate biopsies with normal histology, and the quantity and quality of the products were compared using spectrophotometry and Agilent's BioAnalyzer. Student's t-test's and Bland-Altman analyses were performed in order to investigate differences in nucleic acid quantity and quality between the five kits. The best performing extraction kits were subsequently tested on an additional 84 prostate tumor tissues. A Spearman's correlation test and linear regression analyses were performed in order to investigate the impact of tissue age and amount of tissue on nucleic acid quantity and quality.RESULTS: Nucleic acids extracted with RNeasy® FFPE and QIAamp® DNA FFPE Tissue kit had the highest quantity and quality, and was used for extraction from 84 tumor tissues. Nucleic acids were successfully extracted from all biopsies, and the amount of tumor (in millimeter) was found to have the strongest association with quantity and quality of nucleic acids.CONCLUSIONS: To conclude, this study shows that the choice of nucleic acid extraction kit affects the quantity and quality of extracted products. Furthermore, we show that extraction of nucleic acids from archival formalin-fixed prostate biopsies is possible, allowing molecular studies to be performed on this valuable sample collection.
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| 15. |
- Carlsson, Jessica, 1984-
(författare)
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The Potential Role of miR-126 as a Prognostic Biomarker in Renal Cell Carcinoma
- 2018
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Konferensbidrag (refereegranskat)abstract
- Renal cell carcinoma (RCC) is the most common renal tumor, consisting of ~3% of all malignancies worldwide. The prognosis of RCC can vary widely, and detecting patients at risk for recurrence at an early stage could improve the outcome for the patient. The factors used in the clinics today cannot reliably predict the natural history of the disease, thus there is a need for finding new biomarkers that can aid in predicting patient outcome. Several studies indicate that miRNAs are potential candidates as prognostic biomarkers for patients suffering from RCC. The aim of this study was to validate the potential of miR-126 to predict prognosis in a Swedish cohort of RCC patients. Methods: The expression of miR-126 was measured using quantitative PCR (qPCR) in formalin-fixed paraffin-embedded (FFPE) tumor tissue from 116 patients diagnosed with RCC between 1987 and 2010. Results: miR-126 was found to be differentially expressed between malignant and adjacent benign tissue. The expression of miR-126 was also differentially expressed between tumor grades, and stages of RCC. We could furthermore show that in a univariate model, a low expression of miR-126 was associated with shorter time to recurrence of the disease. Conclusion: Our results indicate that miR-126 expression has a potential to be used as a prognostic biomarker for patients suffering from RCC. However, further studies are needed in order to confirm these results.
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| 16. |
- Carlsson, Jessica, 1984-, et al.
(författare)
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The potential role of miR-126, miR-21 and miR-10b as prognostic biomarkers in renal cell carcinoma
- 2019
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:5, s. 4566-4574
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC) is the most commonly diagnosed renal tumor, consisting of ~3% of all malignancies worldwide. The prognosis of RCC can vary widely, and detecting patients at risk of recurrence at an early stage of disease may improve patient outcome. The factors presently used in a clinical setting cannot reliably predict the natural history of the disease. Therefore, there is a requirement to identify novel biomarkers that can aid in predicting patient outcome. Previous studies have indicated that microRNAs (miRNAs/miRs) are potential candidates as prognostic biomarkers for patients suffering from RCC. Consequently, the aims of the present study were to validate the potential of 3 of these miRNAs to predict the prognosis of patients with RCC, and to investigate the stability of endogenous control genes for miRNA studies in RCC tissues. The expression of 7 endogenous controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in formalin-fixed paraffin-embedded tumor and benign tissues from patients suffering from clear cell RCC (ccRCC). The analyses identified RNU48 and U47 as the most stable endogenous controls. The expression of miR-126, miR-21 and miR-10b was analyzed using RT-qPCR in renal tissues from 116 patients diagnosed with ccRCC. All three investigated miRNAs were differentially expressed between malignant and benign tissues. miR-126 and miR-10b were also differentially expressed between grades and stages of ccRCC. In a univariate, but not in a multivariate model, low expression of miR-126 was associated with shorter time to recurrence of the disease. The results of the present study indicate that of the 3 miRNAs investigated, the expression of miR-126 has the strongest potential as a prognostic biomarker for patients suffering from ccRCC.
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| 17. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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Cutibacterium acnes Induces the Expression of Immunosuppressive Genes in Macrophages and is Associated with an Increase of Regulatory T-Cells in Prostate Cancer
- 2021
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Tumors and infectious agents both benefit from an immunosuppressive environment. Cutibacterium acnes (C. acnes) is a bacterium in the normal skin microbiota, which has the ability to survive intracellularly in macrophages and is significantly more common in prostate cancer tissue compared with normal prostate tissue. This study investigated if prostate cancer tissue culture positive for C. acnes has a higher infiltration of regulatory T-cells (Tregs) and if macrophages stimulated with C. acnes induced the expression of immunosuppressive genes that could be linked to an increase of Tregs in prostate cancer. Real-time PCR and enzyme-linked immunosorbent spot assay (ELISA) were used to examine the expression of immunosuppressive genes in human macrophages stimulated in vitro with C. acnes, and associations between the presence of C. acnes and infiltration of Tregs were investigated by statistically analyzing data generated in two previous studies. The in vitro results demonstrated that macrophages stimulated with C. acnes significantly increased their expression of PD-L1, CCL17, and CCL18 mRNA and protein (p ,0.05). In the cohort, Tregs in tumor stroma and tumor epithelia were positively associated with the presence of C. acnes (P = 0.0004 and P = 0.046, respectively). Since the macrophages stimulated with C. acnes in vitro increased the expression of immunosuppressive genes, and prostate cancer patients with prostatic C. acnes infection had higher infiltration of Tregs than their noninfected counterparts, we suggest that C. acnes may contribute to an immunosuppressive tumor environment that is vital for prostate cancer progression.
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| 18. |
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| 19. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer
- 2018
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Ingår i: The Prostate. - Hoboken, USA : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 78:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs ). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer.METHODS: Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area.RESULTS: In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart.CONCLUSIONS: Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established.
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| 20. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer
- 2016
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Ingår i: Infectious Agents and Cancer. - London, United Kingdom : BioMed Central (BMC). - 1750-9378. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.Methods: We included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient's prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.Results: The results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93-11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.Conclusion: The present study provides further evidence for a role of P. acnes in prostate cancer development.
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| 21. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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Infiltration of M2 Macrophages and Regulatory T Cells Plays a Role in Recurrence of Renal Cell Carcinoma
- 2020
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 20, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory T cells (Tregs) and M2 macrophages have been hypothesized to contribute to tumor progression. We found that M2 macrophages and Tregs are associated with more aggressive renal cell carcinoma, and that they have a synergistic effect on clinical outcome. Background: It has been hypothesized that M2 macrophages and regulatory T cells (Tregs) may contribute to tumor progression by suppression of antitumor immunity. Objective: To investigate the association between infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs with clinical outcomes in renal cell carcinoma patients. Design, setting, and participants: A cohort of 346 patients diagnosed with renal cell carcinoma at Örebro University Hospital between 1986 and 2011 was evaluated for CD163+ M2 macrophage and CD4+FOXP3+ Treg infiltration by immunohistochemistry. Outcome measurements and statistical analysis: Associations between clinicopathological features and infiltration of CD163+ M2 macrophages and/or CD4+FOXP3+ Tregs were estimated with chi-square or Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used. Results and limitations: We found that infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs were associated with adverse clinical outcomes. Our data further demonstrate that CD163+ M2 macrophages and CD4+FOXP3+ Tregs colocalize in tumor and normal tissue, and that this colocalization may have synergistic effects on tumor aggressiveness. The use of tissue microarrays rather than whole sections may be viewed as a limitation. Conclusions: Infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs is associated with recurrence of renal cell carcinoma, and colocalization of these cell types may have an association with clinical outcome. Patient summary: The aim of this study was to investigate the association between infiltration of M2 macrophages and regulatory T cells with clinical outcomes in renal cell carcinoma. We demonstrated that renal cell carcinoma patients with high infiltration of both these cell types are at an increased risk of poor clinical outcomes.
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| 22. |
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| 23. |
- Davidsson, Sabina, et al.
(författare)
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PD-L1 Expression in Men with Penile Cancer and its Association with Clinical Outcomes
- 2019
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 2:2, s. 214-221
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been hypothesized that PD-L1 expression in tumor cells and tumor-infiltrating immune (TII) cells may contribute to tumor progression by inhibiting antitumor immunity.Objective: To investigate the association between PD-L1 expression in tumor cells and TII cells and clinical outcomes in penile cancer.Design, setting, and participants: A cohort of 222 men treated for penile squamous cell carcinoma (SqCC) at Örebro University Hospital between 1984 and 2008 with long-term follow-up (median 34 mo) was evaluated for PD-L1 expression in tumor cells and TII cells via immunohistochemistry.Outcome measurements and statistical analysis: Association between clinicopathological features and PD-L1 expression was estimated using χ2 and Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used.Results and limitations: We found that 32.1% of the tumors and 64.2% of the TII cells expressed PD-L1. Our data demonstrate that penile SqCC patients with PD-L1–positive tumor cells or TII cells are at significant risk of lower cancer-specific survival and that the prognostic value of PD-L1 expression was strongest for tumor cell positivity. The use of tissue microarrays rather than whole sections may be viewed as a limitation.Conclusions: Tumor PD-L1 expression independently identifies penile SqCC patients at risk of poor clinical outcomes.Patient summary: We investigated how many patients with penile cancer had tumors that manufactured PD-L1, a protein that decreases the ability of the immune system to fight cancer. We found that up to one-third of penile tumors make this protein. Patients whose tumors make PD-L1 have more aggressive penile cancer and worse clinical outcomes.
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| 24. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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Prevalence of Flp Pili-Encoding Plasmids in Cutibacterium acnes Isolates Obtained from Prostatic Tissue
- 2017
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Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is one of the hallmarks of prostate cancer. The origin of inflammation is unknown, but microbial infections are suspected to play a role. In previous studies, the Gram-positive, low virulent bacterium Cutibacterium (formerly Propionibacterium) acnes was frequently isolated from prostatic tissue. It is unclear if the presence of the bacterium represents a true infection or a contamination. Here we investigated Cutibacterium acnes type II, also called subspecies defendens, which is the most prevalent type among prostatic C. acnes isolates. Genome sequencing of type II isolates identified large plasmids in several genomes. The plasmids are highly similar to previously identified linear plasmids of type I C. acnes strains associated with acne vulgaris. A PCR-based analysis revealed that 28.4% (21 out of 74) of all type II strains isolated from cancerous prostates carry a plasmid. The plasmid shows signatures for conjugative transfer. In addition, it contains a gene locus for tight adherence (tad) that is predicted to encode adhesive Flp (fimbrial low-molecular weight protein) pili. In subsequent experiments a tad locus-encoded putative pilin subunit was identified in the surface-exposed protein fraction of plasmid-positive C. acnes type II strains by mass spectrometry, indicating that the tad locus is functional. Additional plasmid-encoded proteins were detected in the secreted protein fraction, including two signal peptide-harboring proteins; the corresponding genes are specific for type II C. acnes, thus lacking from plasmid-positive type I C. acnes strains. Further support for the presence of Flp pili in C. acnes type II was provided by electron microscopy, revealing cell appendages in tad locus-positive strains. Our study provides new insight in the most prevalent prostatic subspecies of C. acnes, subsp. defendens, and indicates the existence of Flp pili in plasmid-positive strains. Such pili may support colonization and persistent infection of human prostates by C. acnes.
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| 25. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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Soluble Levels of CD163, PD-L1, and IL-10 in Renal Cell Carcinoma Patients
- 2022
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Ingår i: Diagnostics. - : MDPI. - 2075-4418. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- CD163+ M2 macrophages have been suggested to counteract tumor immunity by increasing immunosuppressive mechanisms including PD-L1 and IL-10 expression. Soluble levels of PD-L1, IL-10, and CD163 have been reported as potential biomarkers in various cancers, although the prognostic value in renal cell carcinoma (RCC) has to be further elucidated. In the present study, we measured the levels of sPD-L1, sIL-10, and sCD163 in 144 blood samples from patients with RCC. The levels were determined by using enzyme linked immunosorbent assays. Soluble PD-L1 and CD163 were detectable in 100% of the serum samples, and sCD163 in 22% of the urine samples, while only a minority of the samples had detectable sIL-10. Significantly higher serum levels of sPD-L1 and sCD163 were observed in patients with metastatic disease (p < 0.05). The results also showed that patients with high levels of sPD-L1 in serum had shorter cancer-specific survival compared with patients with low levels (p = 0.002). The results indicate that sPD-L1 most significantly reflects tumor progression in RCC.
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