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一种结合iTRAQ技术和多组学评估以预测结肠癌预后和免疫治疗疗效的新型定量系统。

A Novel Quantification System Combining iTRAQ Technology and Multi-Omics Assessment to Predict Prognosis and Immunotherapy Efficacy in Colon Cancer.

作者信息

Xia Tianyi, Guo Junnan, Zhang Bomiao, Xue Weinan, Deng Shenhui, Liu Yanlong, Cui Binbin

机构信息

Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin Medial University, Harbin, China.

Department of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Bioeng Biotechnol. 2022 Apr 4;10:862619. doi: 10.3389/fbioe.2022.862619. eCollection 2022.

Abstract

Colon cancer is one of the most common cancer types, although it has certain unique genetic features. This study aimed to develop a unique score for assessing prognosis and immunotherapy efficacy using integrated multi-omics analysis. Isobaric tagging for relative and absolute quantification (iTRAQ) based proteomic analysis was used to screen differentially expressed proteins (DEP) between tumor and normal samples. DEP mRNA obtained from TCGA were clustered into different categories to show landscape-related prognosis and function. Following that, DEG was extracted from DEP mRNA, and the DEP-related score (DEPRS) was constructed to investigate the difference in immunotherapy prognosis and sensitivity. Finally, WCGNA, random forest, and artificial neural networks were used to screen for key genes. The prognostic value and protein level of these genes were validated. A total of 243 DEPs were identified through iTRAQ analysis, and the corresponding DEP mRNA was clustered into three. Following a series of tests, 1,577 DEGs were identified from overlapped DEP mRNA clusters and were classified into three gene clusters. The two types of clusters described above shared comparable characteristics in terms of prognosis and function. Then, it was established that a high DEPRS indicated a poor prognosis and DEPRS had significant associations with TMB, MSI status, and immunotherapeutic response. Finally, the key genes HART3 and FBLN2 were identified and were found to be implicated in immunotherapy and prognosis. The development of a DEPRS based on multi-omics analysis will aid in improving our understanding of colon cancer and guiding a more effective immunotherapy strategy. DEPRS and key genes are used as biomarkers in the clinical evaluation of patients.

摘要

结肠癌是最常见的癌症类型之一,尽管它具有某些独特的基因特征。本研究旨在通过整合多组学分析开发一种独特的评分系统,用于评估预后和免疫治疗疗效。基于相对和绝对定量的等压标记(iTRAQ)蛋白质组学分析用于筛选肿瘤样本和正常样本之间的差异表达蛋白(DEP)。从TCGA获得的DEP mRNA被聚类为不同类别,以显示与预后和功能相关的情况。随后,从DEP mRNA中提取差异表达基因(DEG),并构建DEP相关评分(DEPRS),以研究免疫治疗预后和敏感性的差异。最后,使用加权基因共表达网络分析(WCGNA)、随机森林和人工神经网络筛选关键基因。对这些基因的预后价值和蛋白质水平进行了验证。通过iTRAQ分析共鉴定出243个DEP,相应的DEP mRNA被聚类为三类。经过一系列测试,从重叠的DEP mRNA簇中鉴定出1577个DEG,并将其分为三个基因簇。上述两种类型的簇在预后和功能方面具有可比的特征。然后确定,高DEPRS表明预后不良,并且DEPRS与肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)状态和免疫治疗反应显著相关。最后,鉴定出关键基因HART3和FBLN2,并发现它们与免疫治疗和预后有关。基于多组学分析开发DEPRS将有助于提高我们对结肠癌的理解,并指导更有效的免疫治疗策略。DEPRS和关键基因用作患者临床评估中的生物标志物

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f8f/9014007/29c90e001434/fbioe-10-862619-g001.jpg

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