| 1. |
- Sandström Gerdtsson, Anna, et al.
(författare)
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A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma.
- 2015
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Ingår i: International Journal of Proteomics. - : Hindawi Limited. - 2090-2174 .- 2090-2166. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- Background. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with rapid tumor progression and poor prognosis. This study was motivated by the lack of sensitive and specific PDAC biomarkers and aimed to identify a diagnostic, serum protein signature for PDAC. Methods. To mimic a real life test situation, a multicenter trial comprising a serum sample cohort, including 338 patients with either PDAC or other pancreatic diseases (OPD) and controls with nonpancreatic conditions (NPC), was analyzed on 293-plex recombinant antibody microarrays targeting immunoregulatory and cancer-associated antigens. Results. Serum samples collected from different hospitals were analyzed and showed that (i) sampling from five different hospitals could not be identified as a preanalytical variable and (ii) a multiplexed biomarker signature could be identified, utilizing up to 10 serum markers that could discriminate PDAC from controls, with sensitivities and specificities in the 91-100% range. The first protein profiles associated with the location of the primary tumor in the pancreas could also be identified. Conclusions. The results demonstrate that robust enough serum signatures could be identified in a multicenter trial, potentially contributing to the development of a multiplexed biomarker immunoassay for improved PDAC diagnosis.
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| 2. |
- Sandström Gerdtsson, Anna, et al.
(författare)
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Large Extracellular Vesicle Characterization and Association with Circulating Tumor Cells in Metastatic Castrate Resistant Prostate Cancer
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:1056
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Tidskriftsartikel (refereegranskat)abstract
- Liquid biopsies hold potential as minimally invasive sources of tumor biomarkers for diagnosis, prognosis, therapy prediction or disease monitoring. We present an approach for parallel single-object identification of circulating tumor cells (CTCs) and tumor-derived large extracellular vesicles (LEVs) based on automated high-resolution immunofluorescence followed by downstream multiplexed protein profiling. Identification of LEVs >6 µm in size and CTC enumeration was highly correlated, with LEVs being 1.9 times as frequent as CTCs, and additional LEVs were identified in 73% of CTC-negative liquid biopsy samples from metastatic castrate resistant prostate cancer. Imaging mass cytometry (IMC) revealed that 49% of cytokeratin (CK)-positive LEVs and CTCs were EpCAM-negative, while frequently carrying prostate cancer tumor markers including AR, PSA, and PSMA. HSPD1 was shown to be a specific biomarker for tumor derived circulating cells and LEVs. CTCs and LEVs could be discriminated based on size, morphology, DNA load and protein score but not by protein signatures. Protein profiles were overall heterogeneous, and clusters could be identified across object classes. Parallel analysis of CTCs and LEVs confers increased sensitivity for liquid biopsies and expanded specificity with downstream characterization. Combined, it raises the possibility of a more comprehensive assessment of the disease state for precise diagnosis and monitoring.
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| 3. |
- Sandström Gerdtsson, Anna, et al.
(författare)
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Overexpression of the key metabolic protein CPT1A defines mantle cell lymphoma patients with poor response to standard high dose chemotherapy independent of MIPI and complement established high-risk factors
- 2023
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 108:4, s. 1092-1104
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Tidskriftsartikel (refereegranskat)abstract
- The variable outcome to standard immunochemotherapy for mantle cell lymphoma (MCL) patients is a clinical challenge. Established risk factors, including high MCL international prognostic index (MIPI), high proliferation (Ki-67), non-classic (blastoid/pleomorphic) morphology, and mutated TP53, only partly identify patients in need of alternative treatment. Deepened understanding of biological factors that influence time to progression and relapse would allow for an improved stratification, and identification of novel targets for high-risk patients. We performed gene expression analyses to identify pathways and genes associated with outcome in a cohort of homogeneously treated patients. In addition to deregulated proliferation, we show that thermogenesis, fatty acid degradation and oxidative phosphorylation are altered in patients with poor survival, and that high expression of carnitine palmitoyltransferase 1A (CPT1A), an enzyme involved in fatty acid degradation, can specifically identify high-risk patients independent of the established high-risk factors. We suggest that complementary investigations of metabolism may increase the accuracy of patient stratification and that immunohistochemistry-based assessment of CPT1A can contribute to defining high-risk MCL.
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| 4. |
- Dexlin Mellby, Linda, et al.
(författare)
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Design of recombinant antibody microarrays for membrane protein profiling of cell lysates and tissue extracts.
- 2011
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Ingår i: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 11, s. 1550-1554
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Tidskriftsartikel (refereegranskat)abstract
- Generating global protein expression profiles, including also membrane proteins, will be crucial for our understanding of biological processes in health and disease. In this study, we have expanded our antibody microarray technology platform and designed the first human recombinant antibody microarray for membrane proteins targeting crude cell lysates and tissue extracts. We have optimized all key technological parameters and successfully developed a setup for extracting, labeling and analyzing non-fractionated membrane proteomes under non-denaturing conditions. Finally, the platform was also extended and shown to be compatible with simultaneous profiling of both membrane proteins and water-soluble proteins.
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| 5. |
- Dexlin Mellby, Linda, et al.
(författare)
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Tissue proteome profiling of preeclamptic placenta using recombinant antibody microarrays
- 2010
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Ingår i: Proteomics Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 4:10-11, s. 794-807
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: preeclampsia (PE) is a severe, multi-system pregnancy disorder of yet unknown cause, missing means of treatment, and our fundamental understanding of the disease is still impaired. The purpose of this discovery study was to define candidate placenta tissue protein biomarker signatures to further decipher the molecular features of PE.EXPERIMENTAL DESIGN: we used recombinant antibody microarrays for multiplexed protein expression profiling of preeclamptic placenta tissue (n=25) versus normal placenta (n=11) targeting mainly immunoregulatory water-soluble proteins and membrane proteins. Furthermore, the three known subgroups of PE were profiled, including women with early onset preeclampsia and late onset preeclampsia, as well as women with PE and bilateral notching and intrauterine growth restrictions.RESULTS: the data showed that the first generation of candidate PE-associated placenta tissue protein signatures were delineated, indicating that PE (receiver operating characteristics (ROC) AUC value of 0.83) and the subgroups thereof (ROC AUC values ≤ 0.91) could be distinguished. Notably, the data implied that all subgroups, but preeclampsia with bilateral notching and IUGR, could be further classified into novel subsets (ROC AUC values of 1.0) displaying different inflammatory signatures.CONCLUSIONS AND CLINICAL RELEVANCE: we have taken one step further toward de-convoluting the complex features of PE at the molecular level using affinity proteomics.
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| 6. |
- El-Schich, Zahra, et al.
(författare)
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Interfacing antibody-based microarrays and digital holography enables label-free detection for loss of cell volume
- 2015
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Ingår i: Future Science OA. - : Future Science Group. - 2056-5623. ; 1:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: We introduce the combination of digital holographic microscopy (DHM) and antibody microarrays as a powerful tool to measure morphological changes in specifically antibody-captured cells. The aim of the study was to develop DHM for analysis of cell death of etoposide-treated suspension cells. Result/Methodology: We demonstrate that the cell number, mean area, thickness, and volume were non-invasively measured by using DHM. The cell number was stable over time, but the two cell lines showed changes of cell area and cell irregularity after treatment. The cell volume in etoposide-treated cells was decreased, whereas untreated cells showed stable volume. Conclusions: Our results provide proof of concept for using DHM combined with antibody-based microarray technology for detecting morphological changes in captured cells.
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| 7. |
- Gerdtsson, Anna Sandström, et al.
(författare)
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Plasma protein profiling in a stage defined pancreatic cancer cohort – Implications for early diagnosis
- 2016
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 10:8, s. 1305-1316
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is a disease where detection preceding clinical symptoms significantly increases the life expectancy of patients. In this study, a recombinant antibody microarray platform was used to analyze 213 Chinese plasma samples from PDAC patients and normal control (NC) individuals. The cohort was stratified according to disease stage, i.e. resectable disease (stage I/II), locally advanced (stage III) and metastatic disease (stage IV). Support vector machine analysis showed that all PDAC stages could be discriminated from controls and that the accuracy increased with disease progression, from stage I to IV. Patients with stage I/II PDAC could be discriminated from NC with high accuracy based on a plasma protein signature, indicating a possibility for early diagnosis and increased detection rate of surgically resectable tumors.
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| 8. |
- Kolenčík, Drahomir, et al.
(författare)
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Circulating Tumor Cell Kinetics and Morphology from the Liquid Biopsy Predict Disease Progression in Patients with Metastatic Colorectal Cancer Following Resection
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- The liquid biopsy has the potential to improve current clinical practice in oncology byproviding real-time personalized information about a patient’s disease status and response to treatment. In this study, we evaluated 161 peripheral blood (PB) samples that were collected aroundsurgical resection from 47 metastatic colorectal cancer (mCRC) patients using the High-DefinitionSingle Cell Assay (HDSCA) workflow. In conjunction with the standard circulating tumor cell (CTC)enumeration, cellular morphology and kinetics between time-points of collection were considered inthe survival analysis. CTCs, CTC-Apoptotic, and CTC clusters were found to indicate poor survivalwith an increase in cell count from pre-resection to post-resection. This study demonstrates thatCTC subcategorization based on morphological differences leads to nuanced results between thesubtypes, emphasizing the heterogeneity within the CTC classification. Furthermore, we show thatfactoring in the time-point of each blood collection is critical, both for its static enumeration and forthe change in cell populations between draws. By integrating morphology and time-based analysisalongside standard CTC enumeration, liquid biopsy platforms can provide greater insight into thepathophysiology of mCRC by highlighting the complexity of the disease across a patient’s treatment.
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| 9. |
- Ouyang, Huaqiang, et al.
(författare)
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Is lung involvement a favorable prognostic factor for pancreatic ductal adenocarcinoma with synchronous liver metastases?—A propensity score analysis
- 2023
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Ingår i: Expert Review of Gastroenterology and Hepatology. - : Informa UK Limited. - 1747-4124 .- 1747-4132.
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFor advanced pancreatic cancer, pulmonary metastases (PM) have been considered favorable factors compared to metastases of other sites, but it remains unknown whether the prognosis of patients with synchronous liver and lung metastases is better than that of non-PM.MethodsData was derived from a two-decade cohort and included 932 cases of pancreatic adenocarcinoma with synchronous liver metastases (PACLM). Propensity score matching (PSM) was applied to balance 360 selected cases, grouped into PM (n = 90) and non-PM (n = 270). Overall survival (OS) and survival-related factors were analyzed.ResultsIn PSM-adjusted data, the median OS was 7.3 and 5.8 months, for PM and non-PM, respectively (p = 0.16). Multivariate analysis revealed that male gender, poor performance status, higher hepatic tumor burden, ascites, elevated carbohydrate antigen 19–9, and lactate dehydrogenase were factors of poor survival (p < 0.05). Chemotherapy was the only independent significant factor of favorable prognosis (p < 0.05).ConclusionAlthough lung involvement was indicated to be a favorable prognostic factor for patients with PACLM in the whole cohort, PM were not associated with better survivals in the subset of cases subjected to PSM adjustment.
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