Identification of prognostic biomarkers for cholangiocarcinoma by combined analysis of molecular characteristics of clinical MVI subtypes and molecular subtypes

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-06-18 DOI:10.1016/j.ygeno.2024.110889

Ming-Yue Li , Ya-Hui Liu , Feng Wei , Ping Zhang , Xiao-Dong Sun , Meng Wang , Xiao-Hong Du , Jun-Feng Ye , Wei Qiu , Xiao-Ju Shi , Bai Ji , Ying-Chao Wang , Chao Jiang , Wen-Gang Chai , Bo Huang , Xing-Kai Liu , Qing-Min Chen , Yu Fu , Xin-Tong Hu , Li-Guo Chen , Guo-Yue Lv

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Abstract

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

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通过联合分析临床 MVI 亚型和分子亚型的分子特征，确定胆管癌的预后生物标志物。

胆管癌（CCA）因其恶性程度高、进展迅速和治疗方案有限而广受关注。本研究对来自不同解剖位置的 417 个 CCA 样本的转录组数据进行了分析。研究比较了脂质代谢相关基因和免疫相关基因作为 CCA 分类器的效果。关键基因来自 MVI 亚型和更好的分子亚型。在 MVI 阳性组中，上皮间质转化（EMT）和细胞周期等通路被显著激活。根据脂质代谢（免疫）相关基因，CCA 患者被分为三（四）个亚型，其中脂质代谢-C1、免疫-C2 和免疫-C4 的预后较好。IPTW 分析发现，在校正前后，脂质代谢-C1 的预后明显优于脂质代谢-C2 + C3。KRT16最终被选为关键基因。KRT16的敲除抑制了CCA细胞的增殖、迁移和侵袭。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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