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A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome.

ABSTRACT: The collection of proteins secreted from a cell-the secretome-is of particular interest in cancer pathophysiology due to its diagnostic potential and role in tumorigenesis. However, cancer secretome studies are often limited to one tissue or cancer type or focus on biomarker prediction without exploring the associated functions. We therefore conducted a pan-cancer analysis of secretome gene expression changes to identify candidate diagnostic biomarkers and to investigate the underlying biological function of these changes. Using transcriptomic data spanning 32 cancer types and 30 healthy tissues, we quantified the relative diagnostic potential of secretome proteins for each cancer. Furthermore, we offer a potential mechanism by which cancer cells relieve secretory pathway stress by decreasing the expression of tissue-specific genes, thereby facilitating the secretion of proteins promoting invasion and proliferation. These results provide a more systematic understanding of the cancer secretome, facilitating its use in diagnostics and its targeting for therapeutic development.

SUBMITTER: Robinson JL

PROVIDER: S-EPMC6441842 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome.

Robinson Jonathan L JL Feizi Amir A Uhlén Mathias M Nielsen Jens J

Cell reports 20190301 10

The collection of proteins secreted from a cell-the secretome-is of particular interest in cancer pathophysiology due to its diagnostic potential and role in tumorigenesis. However, cancer secretome studies are often limited to one tissue or cancer type or focus on biomarker prediction without exploring the associated functions. We therefore conducted a pan-cancer analysis of secretome gene expression changes to identify candidate diagnostic biomarkers and to investigate the underlying biologica ...[more]

PMID: 30840886

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Project description:BACKGROUND:The identification of appropriate biomarkers is essential to support important clinical decisions in patients with prostate cancer. The aim of our study was a systematic bioinformatical analysis of the mRNA expression of all genes available for the prostate adenocarcinoma cohort of The Cancer Genome Atlas (TCGA), regarding their potential prognostic and diagnostic role. METHODS:The study cohort comprises 499 patients (TCGA prostate cancer cohort). mRNA expression data were available for approx. 20,000 genes. The bioinformatical statistical pipeline addressed gene expression differences in tumor vs. benign prostate tissue (including gene set enrichment analysis, GSEA) in samples from tumors with different aggressivenesses (Gleason score), as well as prognostic values in multistep survival analyses. RESULTS:Among all genes analyzed, 1754 were significantly downregulated and 1553 genes were significantly upregulated in tumor tissue. In GSEA, 16 of 30 top enriched biological processes were alterations of epigenetic regulation at different levels. Significant correlation with Gleason Score was evident for 8724 genes (range of Pearson r-values 0.09-0.43; all p < 0.05). In univariate Cox regression analyses, mRNA expression of 3571 genes showed statistically significant association with biochemical recurrence-free survival with a range of hazard ratios 0.3-3.8 (p-value 7.4e- 07 to 0.05). Among these, 571 genes were independently associated with biochemical recurrence in multivariate analysis. Access to the full database including results is provided as supplement. CONCLUSIONS:In our systematic analysis we found a big number of genes of potential diagnostic and prognostic value, many of which have not been studied in prostate cancer to date. Due to the comprehensive nature of this analysis and free access to the results, this study represents a reference database for prostate cancer researchers which can be used as a powerful tool for validation purposes and planning of new studies.

Dataset Information

A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome.

Publications

A Systematic Investigation of the Malignant Functions and Diagnostic Potential of the Cancer Secretome.

Similar Datasets

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