Quantitative analysis of the mitochondrial proteome in human ovarian carcinomas

Abstract

Mitochondria play important roles in growth, signal transduction, division, tumorigenesis and energy metabolism in epithelial ovarian carcinomas (EOCs) without an effective biomarker. To investigate the proteomic profile of EOC mitochondrial proteins, a 6-plex isobaric tag for relative and absolute quantification (iTRAQ) proteomics was used to identify mitochondrial expressed proteins (mtEPs) in EOCs relative to controls, followed by an integrative analysis of the identified mtEPs and the Cancer Genome Atlas (TCGA) data from 419 patients. A total of 5115 quantified proteins were identified from purified mitochondrial samples, and 262 proteins were significantly related to overall survival in EOC patients. Furthermore, 63 proteins were identified as potential biomarkers for the development of an EOC, and our findings were consistent with previous reports on a certain extent. Pathway network analysis identified 70 signaling pathways. Interestingly, the results demonstrated that cancer cells exhibited an increased dependence on mitophagy, such as peroxisome, phagosome, lysosome, valine, leucine and isoleucine degradation and fatty acid degradation pathways, which might play an important role in EOC invasion and metastasis. Five proteins (GLDC, PCK2, IDH2, CPT2 and HMGCS2) located in the mitochondrion and enriched pathways were selected for further analysis in an EOC cell line and tissues, and the results confirmed reliability of iTRAQ proteomics. These findings provide a large-scale mitochondrial proteomic profiling with quantitative information, a certain number of potential protein biomarkers and a novel vision in the mitophagy bio-mechanism of a human ovarian carcinoma.