A transcriptome based molecular classification scheme for cholangiocarcinoma and subtype-derived prognostic biomarker

Zhongqi Fan, Xinchen Zou, Guangyi Wang, Yahui Liu, Yanfang Jiang, Haoyan Wang, Ping Zhang, Feng Wei, Xiaohong Du, Meng Wang, Xiaodong Sun, Bai Ji, Xintong Hu, Liguo Chen, Peiwen Zhou, Duo Wang, Jing Bai, Xiao Xiao, Lijiao Zuo, Xuefeng Xia, Xin Yi and Guoyue Lv ()
Additional contact information
Zhongqi Fan: The First Hospital of Jilin University
Xinchen Zou: Peking University Medical Industrial Park, Zhongguancun Life Science Park
Guangyi Wang: The First Hospital of Jilin University
Yahui Liu: The First Hospital of Jilin University
Yanfang Jiang: The First Hospital of Jilin University
Haoyan Wang: Peking University Medical Industrial Park, Zhongguancun Life Science Park
Ping Zhang: The First Hospital of Jilin University
Feng Wei: The First Hospital of Jilin University
Xiaohong Du: The First Hospital of Jilin University
Meng Wang: The First Hospital of Jilin University
Xiaodong Sun: The First Hospital of Jilin University
Bai Ji: The First Hospital of Jilin University
Xintong Hu: The First Hospital of Jilin University
Liguo Chen: The First Hospital of Jilin University
Peiwen Zhou: The First Hospital of Jilin University
Duo Wang: The First Hospital of Jilin University
Jing Bai: Peking University Medical Industrial Park, Zhongguancun Life Science Park
Xiao Xiao: Geneplus-Shenzhen, No.14 Zhongxing Road, Pingshan District
Lijiao Zuo: Peking University Medical Industrial Park, Zhongguancun Life Science Park
Xuefeng Xia: Peking University Medical Industrial Park, Zhongguancun Life Science Park
Xin Yi: Peking University Medical Industrial Park, Zhongguancun Life Science Park
Guoyue Lv: The First Hospital of Jilin University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Previous studies on the molecular classification of cholangiocarcinoma (CCA) focused on certain anatomical sites, and disregarded tissue contamination biases in transcriptomic profiles. We aim to provide universal molecular classification scheme and prognostic biomarker of CCAs across anatomical locations. Comprehensive bioinformatics analysis is performed on transcriptomic data from 438 CCA cases across various anatomical locations. After excluding CCA tumors showing normal tissue expression patterns, we identify two universal molecular subtypes across anatomical subtypes, explore the molecular, clinical, and microenvironmental features of each class. Subsequently, a 30-gene classifier and a biomarker (called “CORE-37”) are developed to predict the molecular subtype of CCA and prognosis, respectively. Two subtypes display distinct molecular characteristics and survival outcomes. Key findings are validated in external cohorts regardless of the stage and anatomical location. Our study provides a CCA classification scheme that complements the conventional anatomy-based classification and presents a promising prognostic biomarker for clinical application.

Date: 2024
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DOI: 10.1038/s41467-024-44748-8

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