Presentation_1.pptx

Abstract

This study aims to identify differentially expressed proteins related with platinum sensitivity and to find biomarkers for predicting platinum response and survival outcomes in patients with high-grade serous ovarian cancer (HGSOC). Eligible HGSOC patients were divided into platinum-sensitive and platinum-resistant groups according to platinum-free interval (PFI). Tissue protein lysates from tumor tissues were subjected to an in-solution tryptic digest followed by Tandem Mass Tag (TMT)-labeling of the resulting peptides and mass spectrometric analysis. Candidate proteins were identified using differential expressed protein and gene-set enrichment (GSEA) analyses, and confirmed by immunohistochemistry (IHC), and their survival relevance were evaluated in TCGA ovarian cancer cohort. The results showed that there was a significant difference of protein expression profiling between the two patient groups. In the GSEA model, a gene-set of 239 extracellular matrix (ECM)-related proteins was significantly enriched in platinum-sensitive group (NES=3.82, q < 10-5), and this finding was confirmed in TCGA ovarian cancer cohort. Interestingly, an ECM-related gene expression, serpin family A member 10 (SERPINA10), was identified to be significantly positively correlate with overall survival (OS) and progression-free survival (PFS) in TCGA ovarian cancer cohort (all p<0.05). IHC results demonstrated that HGSOC patients with high SERPINA10 expression had longer PFI than the patients with low SERPINA10 expression (9 months vs. 5 months, p=0.038), and the SERPINA10 expression had an AUC value of 0.758 (95%CI =0.612-0.905; p=0.005) to discriminated platinum-sensitive tumors from platinum-resistant group. In conclusion, the results suggested that SERPINA10 could be a promising biomarker for predicting the response and survival in platinum-based chemotherapy of HGSOC.