High Serpin Family A Member 10 Expression Confers Platinum Sensitivity and Is Associated With Survival Benefit in High-Grade Serous Ovarian Cancer: Based on Quantitative Proteomic Analysis

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 differentially expressed protein and gene set enrichment analysis (GSEA) and confirmed by immunohistochemistry (IHC), and their survival relevance was evaluated in The Cancer Genome Atlas (TCGA) ovarian cancer cohort. The results showed that there was a significant difference in the 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 the platinum-sensitive group [normalized enrichment score (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 correlated 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 vs. 5 months, p = 0.038), and the SERPINA10 expression had an area under the receiver operating characteristic curve (AUC) value of 0.758 (95% CI = 0.612–0.905; p = 0.005) to discriminate the platinum-sensitive group from the 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.

The Role of the Extracellular Matrix and Tumor-Infiltrating Immune Cells in the Prognostication of High-Grade Serous Ovarian Cancer

“…This gene plays a role in tumor suppression, cell-growth control, and chemotaxis [ 66 ]. SERPINA10, which encodes a protein that belongs to the serpin family, was recently found to be positively correlated with overall survival OS and PFS in HGSOC [ 67 ]. Moreover, using immunohistochemistry (IHC), the authors demonstrated that HGSOC patients with high SERPINA10 expression had longer platinum-free interval (PFI) than the patients with low expression.…”

Clinical significance and immune infiltration analyses of a novel coagulation-related signature in ovarian cancer

“…6 A). The overview of the seven potential DE-CRGs with prognosis value was listed in Table 2 [ 16 – 23 ]. The expressions of the seven potential prognostic CRGs in OV and normal tissues were presented in Fig.…”

“…SERPINA10, also known as Protein Z-dependent proteinase inhibitor (ZPI), could inhibit activated factor X (FXa) in the coagulation process associated with protein Z (PZ), calcium ions, and cephalin [ 42 ]. Guo and colleagues reported that SERPINA10 was a biomarker for predicting platinum sensitivity and survival benefits for OV, though the underlying mechanism is still unknown [ 16 ]. CD38, a multifunctional transmembrane glycoprotein with ADP-ribosyl cyclase activity, is known to be expressed on platelets [ 43 ].…”