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比较蛋白质组学鉴定出补体成分3介导的免疫反应是结肠癌和直肠癌的关键差异。

Comparative Proteome Identifies Complement Component 3-Mediated Immune Response as Key Difference of Colon Adenocarcinoma and Rectal Adenocarcinoma.

作者信息

Liang Jun-Ze, Liang Xiao-Ling, Zhong Li-Ye, Wu Chu-Tian, Zhang Jing, Wang Yang

机构信息

MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, College of Life Science and Technology, Institute of Life and Health Engineering, Jinan University, Guangzhou, China.

Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, China.

出版信息

Front Oncol. 2021 Feb 15;10:617890. doi: 10.3389/fonc.2020.617890. eCollection 2020.

Abstract

Colorectal cancer (CRC) is one of the most lethal diseases with high morbidity and mortality worldwide. Clinically, tumors located in colon and rectum have diverse prognosis and therapeutic outcome. Here, we performed data mining derived from 20 CRC patient samples to compare proteomic difference between colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ). We found that differential expressed proteins (DEPs) upregulated in COAD were mainly enriched in immune response, moreover, higher immune scores were found in COAD than READ, as calculated by The Cancer Genome Atlas (TCGA) data. To identify the core protein of DEPs with high prognostic value for COAD, we performed topological overlap matrix (TOM) to investigate the hub proteins using 77 immune-relevant DEPs, and identified complement component 3 (C3) as the core protein in the immune-relevant DEPs matrix between the COAD and READ. Moreover, we found that C3 was up-regulated in COAD, and its expression was negatively associated with overall survival of COAD patients but not READ. In conclusion, we identified C3-mediated immune response as key feature to distinguish COAD and READ, and highlighted C3 as potential biomarker with high prognostic value for clinical application, which provided new clue for precise treatment of COAD.

摘要

结直肠癌(CRC)是全球发病率和死亡率都很高的最致命疾病之一。临床上,位于结肠和直肠的肿瘤具有不同的预后和治疗结果。在此,我们对来自20例CRC患者样本的数据进行挖掘,以比较结肠腺癌(COAD)和直肠腺癌(READ)之间的蛋白质组差异。我们发现,在COAD中上调的差异表达蛋白(DEP)主要富集于免疫反应,此外,根据癌症基因组图谱(TCGA)数据计算,COAD的免疫评分高于READ。为了鉴定对COAD具有高预后价值的DEP核心蛋白,我们使用77个免疫相关DEP进行拓扑重叠矩阵(TOM)分析以研究枢纽蛋白,并鉴定出补体成分3(C3)是COAD和READ之间免疫相关DEP矩阵中的核心蛋白。此外,我们发现C3在COAD中上调,其表达与COAD患者的总生存期呈负相关,但与READ患者无关。总之,我们确定C3介导的免疫反应是区分COAD和READ的关键特征,并强调C3作为具有高预后价值的潜在生物标志物在临床应用中的意义,这为COAD的精准治疗提供了新线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3c/7959172/c4a43071f685/fonc-10-617890-g001.jpg

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