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蛋白质组学分析揭示高级别浆液性卵巢癌生存的生物学途径和预测蛋白。

Proteomics analysis to reveal biological pathways and predictive proteins in the survival of high-grade serous ovarian cancer.

机构信息

Department of Epidemiology and Biostatistics, School of Public Health, Harbin Medical University, Harbin, 150086, China.

Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Cardiovascular Institute, Harbin Medical University, Harbin, China.

出版信息

Sci Rep. 2017 Aug 29;7(1):9896. doi: 10.1038/s41598-017-10559-9.

Abstract

High-grade serous ovarian cancer (HGSC) is an aggressive cancer with a worse clinical outcome. Therefore, studies about the prognosis of HGSC may provide therapeutic avenues to improve patient outcomes. Since genome alteration are manifested at the protein level, we integrated protein and mRNA data of ovarian cancer from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) and utilized the sparse overlapping group lasso (SOGL) method, a new mechanism-driven variable selection method, to select dysregulated pathways and crucial proteins related to the survival of HGSC. We found that biosynthesis of amino acids was the main biological pathway with the best predictive performance (AUC = 0.900). A panel of three proteins, namely EIF2B1, PRPS1L1 and MAPK13 were selected as potential predictive proteins and the risk score consisting of these three proteins has predictive performance for overall survival (OS) and progression free survival (PFS), with AUC of 0.976 and 0.932, respectively. Our study provides additional information for further mechanism and therapeutic avenues to improve patient outcomes in clinical practice.

摘要

高级别浆液性卵巢癌(HGSC)是一种侵袭性癌症,临床预后较差。因此,对 HGSC 预后的研究可能为改善患者预后提供治疗途径。由于基因组改变在蛋白质水平上表现出来,我们整合了来自癌症基因组图谱 (TCGA) 和临床蛋白质肿瘤分析联盟 (CPTAC) 的卵巢癌的蛋白质和 mRNA 数据,并利用稀疏重叠组套索 (SOGL) 方法,一种新的机制驱动的变量选择方法,选择与 HGSC 生存相关的失调途径和关键蛋白质。我们发现氨基酸的生物合成是具有最佳预测性能的主要生物学途径(AUC=0.900)。一组三个蛋白质,即 EIF2B1、PRPS1L1 和 MAPK13,被选为潜在的预测蛋白,由这三个蛋白组成的风险评分对总生存期(OS)和无进展生存期(PFS)具有预测性能,AUC 分别为 0.976 和 0.932。我们的研究为进一步的机制和治疗途径提供了额外的信息,以改善临床实践中患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f58e/5575023/fea0590b31f4/41598_2017_10559_Fig1_HTML.jpg

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