Comparative secretome profiling and mutant protein identification in metastatic prostate cancer cells by quantitative mass spectrometry-based proteomics

Abstract

Background: Secreted proteins play an important role in promoting cancer (PCa) cell migration and invasion. Proteogenomics helps elucidate the mechanism of diseases, discover therapeutic targets, and generate biomarkers for diagnosis through protein variations. Materials and Methods: We carried out mass a spectrometry-based proteomic analysis of the conditioned media (CM) from two human prostate cancer cell lines, belonging to different metastatic sites, to identify potential metastatic and/or aggressive factors. Results: We identified a total of 598 proteins, among which 561 were quantified based on proteomic analysis. Among the quantified proteins, 128 were up-regulated and 83 were down-regulated in DU145/PC3 cells. Six mutant peptides were identified in the CM of prostate cancer cell lines using proteogenomics approach. Conclusion: This is the first proteogenomics study in PCa aiming at exploring a new type of metastatic factor, which are mutant peptides, predicting a novel biomarker of metastatic PCa for diagnosis, prognosis and drug targeting. Prostate cancer (PCa) is the second most frequent cancer in men worldwide, with lung cancer topping the list. The American Cancer Society has reported that PCa accounted for approximately 180,890 new cases in 2016, with an estimated 26,120 deaths only in the United States (1).