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

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 pl...

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Autores principales:	Wenwen Guo, Xue He, Jing Ni, Liya Ma, Xianzhong Cheng, Congyang Wang, Xiaoxiang Chen, Yan Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	high-grade serous ovarian cancer platinum sensitivity platinum resistance extracellular matrix SERPINA10 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/47b647bc43bb43738f0d057deee3d6ad
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spelling	oai:doaj.org-article:47b647bc43bb43738f0d057deee3d6ad2021-11-30T11:31:16ZHigh 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 Analysis2234-943X10.3389/fonc.2021.761960https://doaj.org/article/47b647bc43bb43738f0d057deee3d6ad2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.761960/fullhttps://doaj.org/toc/2234-943XThis 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.Wenwen GuoXue HeJing NiLiya MaXianzhong ChengCongyang WangXiaoxiang ChenYan WangFrontiers Media S.A.articlehigh-grade serous ovarian cancerplatinum sensitivityplatinum resistanceextracellular matrixSERPINA10Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	high-grade serous ovarian cancer platinum sensitivity platinum resistance extracellular matrix SERPINA10 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	high-grade serous ovarian cancer platinum sensitivity platinum resistance extracellular matrix SERPINA10 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Wenwen Guo Xue He Jing Ni Liya Ma Xianzhong Cheng Congyang Wang Xiaoxiang Chen Yan Wang 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
description	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.
format	article
author	Wenwen Guo Xue He Jing Ni Liya Ma Xianzhong Cheng Congyang Wang Xiaoxiang Chen Yan Wang
author_facet	Wenwen Guo Xue He Jing Ni Liya Ma Xianzhong Cheng Congyang Wang Xiaoxiang Chen Yan Wang
author_sort	Wenwen Guo
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/47b647bc43bb43738f0d057deee3d6ad
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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

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