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. 2019 Jul-Aug;16(4):273-286.
doi: 10.21873/cgp.20132.

Comparative Proteome Profiling and Mutant Protein Identification in Metastatic Prostate Cancer Cells by Quantitative Mass Spectrometry-based Proteogenomics

Oh Kwang Kwon  1 , Yun-Sok Ha  2   3 , Jun Nyung Lee  2   3 , Sunjoo Kim  4 , Hyesuk Lee  4 , So Young Chun  5 , Tae Gyun Kwon  6   3 , Sangkyu Lee  7
Affiliations

Comparative Proteome Profiling and Mutant Protein Identification in Metastatic Prostate Cancer Cells by Quantitative Mass Spectrometry-based Proteogenomics

Oh Kwang Kwon et al. Cancer Genomics Proteomics. 2019 Jul-Aug.

Abstract

Background/aim: Prostate cancer (PCa) is the most frequent cancer found in males worldwide. The aim of this study was to identify new biomarkers using mutated peptides for the prognosis and prediction of advanced PCa, based on proteogenomics.

Materials and methods: The tryptic peptides were analyzed by tandem mass tag-based quantitative proteomics. Proteogenomics were used to identify mutant peptides as novel biomarkers in advanced PCa.

Results: Using a human database, increased levels of INTS7 and decreased levels of SH3BGRL were found to be associated with the aggressiveness of PCa. Using proteogenomics and a cancer mutation database, 70 mutant peptides were identified in PCa cell lines. Using parallel reaction monitoring, the expression of seven mutant peptides was found to be altered in tumors, amongst which CAPN2 D22E was the most significantly up-regulated mutant peptide in PCa tissues.

Conclusion: Altered mutant peptides present in PCa tissue could be used as new biomarkers in advanced PCa.

Keywords: Prostate cancer; metastasis; mutated peptides; proteogenomics; quantitative proteomics.

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Conflict of interest statement

The Authors report no conflicts of interest. The Authors alone are responsible for the content and writing of this article.

Figures

Figure 1
Figure 1. Schematic workflow of the analysis of proteomics and proteogenomics (A) and flowchart of the strategy used to analyze the MS/MS data (B). The number of proteins regulated in aggressive prostate cancer cells (C).
Figure 2
Figure 2. Venn diagram of differentially expressed proteins (DEPs) in aggressive prostate cancer and functional enrichment analysis.
Figure 3
Figure 3. Volcano plot of the total quantified proteins in prostate cancer with different degrees of aggressiveness (A). Verification of the mRNA levels of INTS7 and SH3BGRL from the cBioPortal database (B) and correlation of the expression of both genes (C). *p<0.05 and **p<0.01.
Figure 4
Figure 4. Schematic of the workflow for the identification and verification of mutant peptides (A). Workflow schematic of the parallel reaction monitoring (PRM) for mutant peptides in prostate cancer tissues (B).
Figure 5
Figure 5. Changes in the relative peak area of mutant peptides between normal and prostate cancer tissue (A) and among normal prostate tissue and prostate cancer tissue from stage T2 and T3 patients (B). Underlining indicates the mutant sites. *p<0.05.
Figure 5
Figure 5. Changes in the relative peak area of mutant peptides between normal and prostate cancer tissue (A) and among normal prostate tissue and prostate cancer tissue from stage T2 and T3 patients (B). Underlining indicates the mutant sites. *p<0.05.
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