Identification and validation of inflammatory subtypes in intrahepatic cholangiocellular carcinoma

作者：Biao Gao, Yafei Wang, Xianzhou Zhang, Hao Jiang, Feng Han, Chonghui Li, Shichun Lu · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-05529-5 · 被引用次数：10 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Liver Diseases and Immunity、Ferroptosis and cancer prognosis

BACKGROUND: Inflammation plays a critical role in tumor development. Inflammatory cell infiltration and inflammatory mediator synthesis cause changes in the tumor microenvironment (TME) in several cancers, especially in intrahepatic cholangiocellular carcinoma (ICC). However, methods to ascertain the inflammatory state of patients using reliable biomarkers are still being explored. METHOD: We retrieved the RNA sequencing and somatic mutation analyses results and the clinical characteristics of 244 patients with ICC from published studies. We performed consensus clustering to identify the molecular subtypes associated with inflammation. We compared the prognostic patterns, clinical characteristics, somatic mutation profiles, and immune cell infiltration patterns across inflammatory subtypes. We performed quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to confirm gene expression. We performed logistic regression analyses to construct a nomogram predicting the inflammatory status of patients with ICC. RESULTS: Our results confirmed that ICC can be categorized into an inflammation-high subtype (IHS) and an inflammation-low subtype (ILS). Patients from each group had distinct prognosis, clinical characteristics, and TME composition. Patients with ICC in the IHS group showed poorer prognosis owing to the immunosuppressive microenvironment and high frequency of KRAS and TP53 mutations. Cancer-associated fibroblast (CAF)-derived COLEC11 reduc...