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. 2020 Apr 8:10:493.
doi: 10.3389/fonc.2020.00493. eCollection 2020.

Quantitative SWATH-Based Proteomic Profiling for Identification of Mechanism-Driven Diagnostic Biomarkers Conferring in the Progression of Metastatic Prostate Cancer (VSports手机版)

Anshika N Singh  1 , Neeti Sharma  2
Affiliations

Quantitative SWATH-Based Proteomic Profiling for Identification of Mechanism-Driven Diagnostic Biomarkers Conferring in the Progression of Metastatic Prostate Cancer

Anshika N Singh et al. Front Oncol. .

"V体育ios版" Abstract

Prostate cancer (PCa), the most frequently diagnosed malignancy in men is associated with significant mortality and morbidity. Therefore, demand exists for the identification of potential biomarkers for patient stratification according to prognostic risks and the mechanisms involved in cancer development and progression to avoid over/under treatment of patients and prevent relapse. Quantitative proteomic mass spectrometry profiling and gene enrichment analysis of TGF-β induced-EMT in human Prostate androgen-dependent (LNCaP) and androgen-independent (PC-3) adenocarcinoma cell lines was performed to investigate proteomics involved in Prostate carcinogenesis and their effect onto the survival of PCa patients VSports手机版. Amongst 1,795 proteins, which were analyzed, 474 proteins were significantly deregulated. These proteins contributed to apoptosis, gluconeogenesis, transcriptional regulation, RNA splicing, cell cycle, and MAPK cascade and hence indicating the crucial roles of these proteins in PCa initiation and progression. We have identified a panel of six proteins viz. , GOT1, HNRNPA2B1, MAPK1, PAK2, UBE2N, and YWHAB, which contribute to cancer development, and the transition of PCa from androgen dependent to independent stages. The prognostic values of identified proteins were evaluated using UALCAN, GEPIA, and HPA datasets. The results demonstrate the utility of SWATH-LC-MS/MS for understanding the proteomics involved in EMT transition of PCa and identification of clinically relevant proteomic biomarkers. .

Keywords: EMT; SWATH; biomarkers; prostate cancer; proteomics. V体育安卓版.

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Figures

Figure 1
Figure 1
(A) Scatter plot of 660 dysregulated proteins, including 2 upregulated and 126 downregulated proteins in Androgen dependent Prostate cancer cell lines. The green dots are representatives of upregulated proteins and red dots represent the downregulated proteins; (B) Scatter plot of 1,135 dysregulated proteins, including 69 upregulated and 277 downregulated proteins in Androgen independent Prostate cancer cell lines. The green dots are representatives of upregulated proteins and red dots represent the downregulated proteins. (C) Heatmap of dysregulated proteins in both Androgen dependent and Androgen independent cell line. The color bar represents the expression levels of the proteins, corresponding to the log2-ratio of fold change.
Figure 2
Figure 2
GO and KEGG pathway enrichment of most significantly regulated proteins in Androgen dependent cell lines post-TGF-β treatment; (A) Top significantly enriched biological processes of deregulated proteins quantified using the SWATH-LC-MS/MS approach; (B) Top significantly enriched protein Molecular processes of deregulated proteins quantified using the SWATH-MS approach; (C) Top significantly enriched Cellular localization of deregulated proteins quantified using the SWATH-LC-MS/MS approach; (D) Top significantly enriched protein class of deregulated proteins quantified using the SWATH-LC-MS/MS approach; GO and KEGG pathway enrichment of most significantly regulated proteins in Androgen independent cell lines post-TGF-β treatment; (E) Top significantly enriched biological processes of deregulated proteins quantified using the SWATH-LC-MS/MS approach; (F) Top significantly enriched protein Molecular processes of deregulated proteins quantified using the SWATH-LC-MS/MS approach; (G) Top significantly enriched Cellular localization of deregulated proteins quantified using the SWATH-MS approach; and (H) Top significantly enriched protein class of deregulated proteins quantified using the SWATH-LC-MS/MS approach.
Figure 3
Figure 3
Comparisons of the expression of the six genes between Prostate cancer (T = 492) and non-Prostate cancer tissues (N = 152) in TCGA and GTEx based on GEPIA. The Y-axis represents the log2(TPM + 1) for gene expression. The gray bar represents the normal (N = 152) non-PCa tissues, and the red bar shows the Prostate cancer (T = 492) tissues. TPM, transcripts per kilobase million; p < 0.05. (A) GOT1, (B) HNRNPA2B1, (C) MAPK1, (D) UBE2N, (E) PAK2, and (F) YWHAB.
Figure 4
Figure 4
Validation of the hub genes from the HPA database. (A) Representative image of Low expression of GOT1 in Prostate tumor cells. (B) Representative image of Medium expression of GOT1 in Prostate tumor cells. (C,D) Representative image of Low expression of PAK2 in Prostate tumor cells. (E,F) Representative image of High expression of HNRNPA2B1 in Prostate tumor cells. (G) Representative image of Medium expression of MAPK1 in Prostate tumor cells. (H) Representative image of High expression of MAPK1 in Prostate tumor cells. (I) Representative image of Low expression of UBE2N in Prostate tumor cells. (J) Representative image of Medium expression of UBE2N in Prostate tumor cells. (K) Representative image of Medium expression of YWHAB in Prostate tumor cells. (L) Representative image of High expression of YWHAB in Prostate tumor cells.
Figure 5
Figure 5
Kaplan Meier patient survival plot based on SWATH-LC-MS/MS protein area of (A) HNRNPA2B1, (B) UBE2N, and (C) PAK2. The red line represents High expression (n = 125) and the blue line represents Low/Medium expression (n = 372).
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References (VSports在线直播)

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. (2018) 68:7–30. 10.3322/caac.21442 - DOI - PubMed
    1. Singh AN, Sharma N. Identification of key pathways and genes with aberrant methylation in prostate cancer using bioinformatics analysis. Onco Targets Ther. (2017) 10:4925. 10.2147/OTT.S144725 - DOI - PMC - PubMed
    1. Loeb S, Bjurlin MA, Nicholson J, Tammela TL, Penson DF, Carter HB, et al. . Overdiagnosis and overtreatment of prostate cancer. Eur Urol. (2014) 65:1046–55. 10.1016/j.eururo.2013.12.062 - DOI - PMC - PubMed
    1. Grant CM, Kyprianou N. Epithelial mesenchymal transition (EMT) in prostate growth and tumor progression. Trans Androl Urol. (2013) 2:202–11. 10.3978/j.issn.2223-4683.2013.09.04 - DOI - PMC - PubMed
    1. Lebrun JJ. The dual role of TGF in human cancer: from tumor suppression to cancer metastasis. ISRN Mol Biol. (2012) 24:2012 10.5402/2012/381428 - DOI - PMC - PubMed