| 1. |
- Boldrup, Linda, et al.
(författare)
-
Evidence that circulating proteins are more promising than miRNAs for identification of patients with squamous cell carcinoma of the tongue
- 2017
-
Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:61, s. 103437-103448
-
Tidskriftsartikel (refereegranskat)abstract
- Despite intense research, squamous cell carcinoma of the tongue remains a devastating disease with a five-year survival of around 60%. Late detection and recurrence are the main causes for poor survival. The identification of circulating factors for early diagnosis and/or prognosis of cancer is a rapidly evolving field of interest, with the hope of finding stable and reliable markers of clinical significance. The aim of this study was to evaluate circulating miRNAs and proteins as potential factors for distinguishing patients with tongue squamous cell carcinoma from healthy controls. Array-based profiling of 372 miRNAs in plasma samples showed broad variations between different patients and did not show any evidence for their use in diagnosis of tongue cancer. Although one miRNA, miR-150, was significantly down-regulated in plasma from patients compared to controls. Surprisingly, the corresponding tumor tissue showed an up-regulation of miR-150. Among circulating proteins, 23 were identified as potential markers of squamous cell carcinoma of the tongue. These findings imply that circulating proteins are a more promising source of biomarkers for tongue squamous cell carcinomas than circulating miRNAs. The data also highlight that circulating markers are not always directly associated with tumor cell properties.
|
|
| 2. |
- Boldrup, Linda, et al.
(författare)
-
Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma
- 2017
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:12, s. 19389-19402
-
Tidskriftsartikel (refereegranskat)abstract
- Due to the high frequency of loco-regional recurrences, which could be explained by changes in the field surrounding the tumor, patients with squamous cell carcinoma of head and neck show poor survival. Here we identified a total of 554 genes as dysregulated in clinically tumor free tongue tissue in patients with tongue tumors when compared to healthy control tongue tissue. Among the top dysregulated genes when comparing control and tumor free tissue were those involved in apoptosis (CIDEC, MUC1, ZBTB16, PRNP, ECT2), immune response (IFI27) and differentiation (KRT36). Data suggest that these are important findings which can aid in earlier diagnosis of tumor development, a relapse or a novel squamous cell carcinoma of the tongue, in the absence of histological signs of a tumor.
|
|
| 3. |
- Gu, Xiaolian, 1976-, et al.
(författare)
-
Copy number variation : A prognostic marker for young patients with squamous cell carcinoma of the oral tongue
- 2019
-
Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 48:1, s. 24-30
-
Tidskriftsartikel (refereegranskat)abstract
- Background The incidence of squamous cell carcinoma of the oral tongue (SCCOT) is increasing in people under age 40. There is an urgent need to identify prognostic markers that help identify young SCCOT patients with poor prognosis in order to select these for individualized treatment. Materials and methods To identify genetic markers that can serve as prognostic markers for young SCCOT patients, we first investigated four young (<= 40 years) and five elderly patients (>= 50 years) using global RNA sequencing and whole-exome sequencing. Next, we combined our data with data on SCCOT from the cancer genome atlas (TCGA), giving a total of 16 young and 104 elderly, to explore the correlations between genomic variations and clinical outcomes. Results In agreement with previous studies, we found that SCCOT from young and elderly patients was transcriptomically and also genomically similar with no significant differences regarding cancer driver genes, germline predisposition genes, or the burden of somatic single nucleotide variations (SNVs). However, a disparate copy number variation (CNV) was found in young patients with distinct clinical outcome. Combined with data from TCGA, we found that the overall survival was significantly better in young patients with low-CNV (n = 5) compared to high-CNV (n = 11) burden (P = 0.044). Conclusions Copy number variation burden is a useful single prognostic marker for SCCOT from young, but not elderly, patients. CNV burden thus holds promise to form an important contribution when selecting suitable treatment protocols for young patients with SCCOT.
|
|
| 4. |
- Gu, Xiaolian, et al.
(författare)
-
Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Epigenetic modifications are essential regulators of biological processes. Decreased DNA methylation of OAS2 (2'-5'-Oligoadenylate Synthetase 2), encoding an antiviral protein, has been seen in psoriasis. To provide further insight into the epigenetic regulation of OAS2, we performed pyrosequencing to detect OAS2 DNA methylation status at 11 promoter and first exon located CpG sites in psoriasis (n = 12) and two common subtypes of squamous cell carcinoma (SCC) of the head and neck: tongue (n = 12) and tonsillar (n = 11). Compared to corresponding controls, a general hypomethylation was seen in psoriasis. In tongue and tonsillar SCC, hypomethylation was found at only two CpG sites, the same two sites that were least demethylated in psoriasis. Despite differences in the specific residues targeted for methylation/demethylation, OAS2 expression was upregulated in all conditions and correlations between methylation and expression were seen in psoriasis and tongue SCC. Distinctive methylation status at four successively located CpG sites within a genomic area of 63 bp reveals a delicately integrated epigenetic program and indicates that detailed analysis of individual CpGs provides additional information into the mechanisms of epigenetic regulation in specific disease states. Methylation analyses as clinical biomarkers need to be tailored according to disease-specific sites.
|
|
| 5. |
- Gu, Xiaolian, 1976-, et al.
(författare)
-
High immune cytolytic activity in tumor-free tongue tissue confers better prognosis in patients with squamous cell carcinoma of the oral tongue
- 2019
-
Ingår i: The journal of pathology. Clinical research. - : John Wiley & Sons. - 2056-4538. ; 5:4, s. 240-247
-
Tidskriftsartikel (refereegranskat)abstract
- Immune cells and cytolytic activity within the tumor microenvironment are being intensively studied. Through transcriptome profiling, immune cell enumeration using the xCell tool and cytolytic activity quantification according to granzyme A (GZMA) and perforin (PRF1) mRNA levels, we investigated immunoreactivity in tumor and/or tumor‐free tongue tissue samples from 31 patients with squamous cell carcinoma of the oral tongue and 14 healthy individuals (control tongue tissues). We found significantly altered immune cell compositions (p < 0.001) and elevated cytolytic activity (p < 0.001) in tumor compared to tumor‐free samples, and altered infiltration of a subset of immune cells (e.g. CD8+ T cells, p < 0.01) as well as increased cytolytic activity (p < 0.001) in tumor‐free compared to control samples. Controlling for patient age at diagnosis and tumor stage, Cox regression analysis showed that high cytolytic activity in tumor‐free samples associated with improved disease‐free survival (hazard ratio= 4.20, 95% CI = 1.09–16.20, p = 0.037). However, the degree of cytolytic activity in tumor samples did not provide prognostic information. Taken together, our results show the presence of cancer‐related immune responses in clinically tumor‐free tongue in patients with squamous cell carcinoma of the oral tongue. Measuring cytolytic activity in tumor‐free tongue samples contralateral to tumor might thus be an effective approach to predict clinical outcome.
|
|
| 6. |
- Mäkitie, Antti A., et al.
(författare)
-
Transoral Robotic Surgery in the Nordic Countries : Current Status and Perspectives
- 2018
-
Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The five Nordic countries with a population of 27 M people form a rather homogenous region in terms of health care. The management of head and neck cancer is centralized to the 21 university hospitals in these countries. Our aim was to gain an overview of the volume and role of transoral robotic surgery (TORS) and to evaluate the need to centralize it in this area as the field is rapidly developing.Materials and Methods: A structured questionnaire was sent to all 10 Departments of Otorhinolaryngology-Head and Neck Surgery in the Nordic countries having an active programme for TORS in December 2017.Results: The total cumulative number of performed robotic surgeries at these 10 Nordic centers was 528 and varied between 5 and 240 per center. The median annual number of robotic surgeries was 38 (range, 5-60). The observed number of annually operated cases remained fairly low (<25) at most of the centers.Conclusions: The present results showing a limited volume of performed surgeries call for considerations to further centralize TORS in the Nordic countries.
|
|
| 7. |
- Sgaramella, Nicola, et al.
(författare)
-
Ethnicity based variation in expression of E-cadherin in patients with squamous cell carcinoma of the oral tongue
- 2018
-
Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 16:5, s. 6603-6607
-
Tidskriftsartikel (refereegranskat)abstract
- The oral tongue is the most common site for tumours within the oral cavity. Despite intense research, there has been no improvement in the survival rate for patients with oral tongue squamous cell carcinoma (OTSCC) during the last decades. Differences between oral cancer patients based on ethno-geographical distribution have been reported. The present study used immunohistochemistry to evaluate commonly used markers of cancer cell phenotypes, E-cadherin, -catenin and cytokeratins 5 and 19, in 120 patients with OTSCC. To evaluate the impact of ethnicity, patients from Sweden and Italy were included. A higher proportion of Swedish patients exhibited high expression of E-cadherin in their tumours (P=0.039), and high levels of E-cadherin in Swedish OTSCC patients that had succumbed to their disease were associated with poor prognosis. These data demonstrated differences in the pathological characteristics of OTSCC between two different European populations. The findings emphasise the need to take ethnicity/geographical location of patients into account when comparing results from different studies of OTSCC.
|
|
| 8. |
- Sgaramella, Nicola, et al.
(författare)
-
Searching for new targets and treatments in the battle against squamous cell carcinoma of the head and neck, with specific focus on tumours of the tongue
- 2018
-
Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers. - 1568-0266 .- 1873-4294. ; 18:3, s. 214-218
-
Forskningsöversikt (refereegranskat)abstract
- Squamous cell carcinoma of the head and neck, SCCHN, is a heterogeneous group of tumours not only concerning the site of origin but also regarding aetiology. The 5-year survival for the whole group of SCCHN tumours has not significantly improved over the last 20-25 years. Apart from tumour spread to lymph nodes, N status, gains and losses of specific chromosomes are the only factors shown to be independent prognostic markers for these tumours. Worldwide, an increasing number of people ≤ 40 years are seen being affected by tongue SCC, the most common tumour within the SCCHN group. Even without any clinical signs of metastasis, up to 30% of all tongue SCC have histologically detectable spread to lymph nodes. In this mini review, field cancerization, tumour microenvironment, the so called EMT (epithelial mesenchymal transition) process and the role of viruses in development of SCCHN are discussed as well as potential new therapeutic targets. For the group of tongue SCC, with the increasing incidence seen in young patients and particularly women, new data with impact on prognosis and treatment are urgently needed. But as long as data from the analyses of several sub sites are presented as valid for the whole group of tumours, this vital point is missed.
|
|
| 9. |
- Strindlund, Klas, et al.
(författare)
-
Patients with high c-MYC-expressing squamous cell carcinomas of the tongue show better survival than those with low- and medium-expressing tumours
- 2017
-
Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 46:10, s. 967-971
-
Tidskriftsartikel (refereegranskat)abstract
- Backgroundc-MYC is a potent oncoprotein with roles in a wide range of cellular processes such as differentiation, apoptosis and growth control. Deregulation of the MYC gene is commonly seen in human tumours resulting in overexpression of the protein. Here we studied expression of c-MYC in correlation to clinical outcome in patients with primary squamous cell carcinoma of the mobile tongue. MethodsImmunohistochemistry was used to identify c-MYC in a group of 104 tongue squamous cell carcinomas with an antibody directed against the N-terminal part of the protein. Staining was evaluated by multiplying the percentage of c-MYC-expressing cells with staining intensity, giving a quick score for each tumour. ResultsAll 104 tumours expressed c-MYC at varying levels. Quantitation according to per cent of positive cells and staining intensity revealed that most (15/21; 71%) high-expressing tumours were seen in males. Within the group of high c-MYC-expressing tumours, the majority were alive 2 and 5 years after treatment. ConclusionsThe present findings show that expression of c-MYC has prognostic value in squamous cell carcinoma of the tongue, and could be useful in choice of therapy.
|
|
| 10. |
- van der Wal, Jacqueline E., et al.
(författare)
-
High podoplanin and low E-cadherin levels correlate with better prognosis in adenoid cystic carcinoma
- 2019
-
Ingår i: Clinical and Experimental Dental Research. - : Wiley. - 2057-4347. ; 5:4, s. 350-355
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: As tumour spread is a complicating event for malignant salivary gland tumours, we decided to study factors related to cell adhesion and lymph vessel formation in two of the three most common malignant salivary gland tumours, mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC), to clarify the clinical relevance and potential usefulness of these factors. We also included a group of polymorphous adenocarcinoma (PAC) as this tumour, in common with ACC often shows perineural growth, but in contrast to ACC has an overall good prognosis.Material and methods: Eighteen patients with ACC, 15 with MEC, and six with PAC were included. Protein expression of podoplanin and E‐cadherin was evaluated as percentage of cells expressing the protein and intensity of expression. Ki‐67 expression was included in the study as a marker of proliferative activity.Results: Looking at podoplanin, significantly more ACCs were high expressing compared with both MECs (P = .001) and PACs (P = .028). Also when looking at Ki‐67 expression, significantly more ACCs were high expressing compared with MECs (P = .003). Significantly better survival was also seen for ACCs with high podoplanin (P = .022) and low E‐cadherin expression (P = .021), respectively.Conclusions: Our findings show that ACCs express significantly higher levels of podoplanin compared with both MECs and PACs and that high levels are correlated to better survival. Even though the group of PACs analysed was small, these tumours, despite their tendency to perineural spread, which they have in common with ACC, differ from ACCs concerning expression of factors with a known connection to tumour spread.
|
|
