Dataset Information

Prostate cancer tissue proteomics

ABSTRACT: Prostate cancer (PCa) is a non-cutaneous malignancy that is the most frequent cancer found in males worldwide, and its mortality rate is increasing every year. Although, PCa grows slowly and is not a threat to survival, advanced PCa, metastatic PCa, is aggressive form of PCa and can spread to other organs, resulting in the 5-year survival rate dropping to 30%. However, there are no molecular markers for advanced and/or aggressive PCa, and it is an urgent clinically need to find biomarkers for prognosis and prediction of advanced PCa. Here, we used mass spectrometry-based proteomics to discover new biomarkers for prognosis and prediction of advanced PCa in tissue obtained from PCa patients who were diagnosed with T2, T3 and metastasis in regional lymph nodes. We identified 1,904 proteins and 1,673 proteins were quantified from PCa tissues, respectively. In particular, 344 differentially expressed proteins (DEP) of which 124 were up-regulated and 216 were down-regulated were listed. From PLS-DA score plotting using SIMCA P+ software and GO and KEGG enrichment analysis by DAVID, we also propose SRM, NOLC1, and PTGIS, which we found through this proteomics analysis, as representing new protein biomarkers for diagnosis of advanced PCa. The proteomics results were verified by immunoblotting assay in metastatic PCa cell-lines and indirect ELISA in prostate specimens. In particular, SRM is significantly increased depending on cancer progress stages, so the possibility of biomarker for prognosis and prediction of advanced PCa is confirmed.

INSTRUMENT(S): LTQ Orbitrap, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Prostate Gland

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Oh Kwang Kwon

LAB HEAD: Sangkyu Lee

PROVIDER: PXD013422 | Pride | 2020-03-04

REPOSITORIES: Pride

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Publications

Identification of Novel Prognosis and Prediction Markers in Advanced Prostate Cancer Tissues Based on Quantitative Proteomics.

Kwon Oh Kwang OK Ha Yun-Sok YS Na Ann-Yae AY Chun So Young SY Kwon Tae Gyun TG Lee Jun Nyung JN Lee Sangkyu S

Cancer genomics & proteomics 20200301 2

<h4>Background/aim</h4>Prostate cancer (PCa) is the most frequent cancer found in males worldwide, and its mortality rate is increasing every year. However, there are no known molecular markers for advanced or aggressive PCa, and there is an urgent clinical need for biomarkers that can be used for prognosis and prediction of PCa.<h4>Materials and methods</h4>Mass spectrometry-based proteomics was used to identify new biomarkers in tissues obtained from patients with PCa who were diagnosed with T ...[more]

PMID: 32108042

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Project description:Prostate cancer (PCa) remains the malignancy with the highest morbidity in men (1). Although early-stage PCa usually causes no symptoms, cancer cells in prostate glands readily metastasize to bones, lymph nodes, lungs, and liver during PCa progression (2). Common strategies, including surgery, radiation therapy, and androgen-deprivation therapy, are promising treatments for early-stage PCa. However, advanced PCa still lacks effective therapeutic strategies (3-5). Thus, researchers are currently focused on inhibiting tumor progression to explore effective therapeutic strategies for PCa treatment (6, 7). Cancer-associated fibroblasts (CAFs), stromal cells derived from normal fibroblasts or epithelia, are one of the major cellular components in the tumor microenvironment (8, 9). Compared with normal fibroblasts, CAFs are activated with increased expression of key protein markers, such as α-SMA, FAP, vimentin and S100A4 protein (10, 11). In the tumor microenvironment, CAFs secrete various growth effectors or cytokines to the extracellular matrix and thereby promote tumor progression by directly enhancing cancer cell growth, angiogenic induction, the extracellular matrix modification, and tumor-promoting inflammatory mediation (11-14). Notably, CAFs could act as an immunosuppressive mediator for the formation of an immunosuppressive tumor environment by recruiting and activating multiple immune cells (15). As such, CAFs might be a potential target in anti-tumor immunotherapy (16, 17). Currently, increased research has focused on inhibiting the immunosuppressive function of prostate cancer-associated fibroblasts (prostate CAFs), which may suggest therapeutic strategies for PCa (18, 19). Polysaccharides from Lentinus edodes are known to exhibit potent anti-tumor and immunomodulatory functions. The anti-tumor mechanisms of L. edodes polysaccharides include regulating the innate immune system by mediating CAF function, preventing tumorigenesis, or directly killing tumor cells via cell cycle regulation or apoptotic induction (20-22). Our previous studies isolated a novel polysaccharide component (MPSSS) from L. edodes. We found the secretome of prostate CAFs treated with MPSSS could inhibit the proliferation of CD4+ and CD8+ T cells, which suggested that MPSSS could prevent the immunosuppressive function of prostate CAFs (22). However, although the secretome of MPSSS-treated prostate CAFs inhibit the proliferation of T cells, how the secretome of MPSSS-treated prostate CAFs affect PCa progression is still unclear. The secretome defines as all proteins secreted by the organism or living cells into the extracellular space, which consists of soluble proteins and extracellular vesicles (EVs) (23). The secretome of prostate CAFs pays vital roles in PCa tumor origination, progression (24, 25). Since EVs contains various molecules (proteins, RNA, DNA and lipid) (26), we speculate that soluble proteins and EVs of prostate CAFs might have the different influence on PCa cells. In this study, the secretome of prostate CAFs untreated/treated with MPSSS were separated into the high molecular weight secretome (>100 kD) and the low molecular weight secretome (3-100 kD) using 100 kD and 3kD MWCO memberane filtration to narrow down the range of active components. The high molecular weight secretome contained extracellular vesicles (EVs) and large soluble proteins, while the low molecular weight secretome contained the small soluble proteins. The secretome of prostate CAFs untreated/treated with MPSSS were used to explore the underlying function and molecular mechanism using quantitative proteomics and multiple biochemical approaches.

Dataset Information

Prostate cancer tissue proteomics

Publications

Identification of Novel Prognosis and Prediction Markers in Advanced Prostate Cancer Tissues Based on Quantitative Proteomics.

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