Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China.
Geneplus-Beijing Institute, 9th Floor, No.6 Building, Peking University Medical Industrial Park, Zhongguancun Life Science Park, Beijing, China.
Nat Commun. 2024 Jan 11;15(1):484. doi: 10.1038/s41467-024-44748-8.
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.
先前关于胆管癌（CCA）的分子分类研究集中在某些解剖部位，忽略了转录组谱中的组织污染偏差。我们旨在为跨解剖部位的 CCA 提供通用的分子分类方案和预后生物标志物。对来自不同解剖部位的 438 例 CCA 病例的转录组数据进行全面的生物信息学分析。在排除显示正常组织表达模式的 CCA 肿瘤后，我们确定了两种跨解剖亚型的通用分子亚型，探索了每个类别的分子、临床和微环境特征。随后，开发了一个 30 基因分类器和一个生物标志物（称为“CORE-37”），分别用于预测 CCA 的分子亚型和预后。两种亚型显示出不同的分子特征和生存结果。无论分期和解剖部位如何，关键发现均在外群中得到验证。我们的研究提供了一个补充传统基于解剖的分类的 CCA 分类方案，并提出了一个有前途的预后生物标志物用于临床应用。
