肝细胞癌
质量细胞仪
免疫系统
多路复用
肿瘤科
医学
肿瘤微环境
内科学
癌症研究
免疫学
表型
生物信息学
生物
基因
生物化学
作者
Yihong Chen,Xiaolei Deng,Lei Yin,Ying Han,Yinghui Peng,Wantao Wu,Xinwen Wang,Jiayao Ma,Erya Hu,Xin Zhou,Edward Shen,Shan Zeng,Changjing Cai,Ya‐Zhen Qin,Hong Shen
标识
DOI:10.1097/hep.0000000000000869
摘要
Tumor microenvironment (TME) heterogeneity leads to a discrepancy in survival prognosis and clinical treatment response for hepatocellular carcinoma (HCC) patients. The clinical applications of documented molecular subtypes are constrained by several issues.We integrated three single-cell datasets to describe the TME landscape and identified six prognosis-related cell subclusters. Unsupervised clustering of subcluster-specific markers was performed to generate transcriptomic subtypes. The predictive value of these molecular subtypes for prognosis and treatment response was explored in multiple external HCC cohorts and the Xiangya HCC cohort. TME features were estimated using single-cell immune repertoire sequencing, mass cytometry and multiplex immunofluorescence. The prognosis-related score (PRS) was constructed based on machine learning algorithm. Comprehensive single-cell analysis described TME heterogeneity in HCC. The five transcriptomic subtypes possessed different clinical prognoses, stemness characteristics, immune landscapes and therapeutic responses. Class 1 exhibited an inflamed phenotype with better clinical outcomes, while Classes 2 and 4 were characterized by a lack of T cell infiltration. Classes 5 and 3 indicated an inhibitory tumor immune microenvironment. Analysis of multiple therapeutic cohorts suggested that Classes 5 and 3 were sensitive to ICB and targeted therapy, whereas Classes 1 and 2 were more responsive to transcatheter arterial chemoembolization treatment. Class 4 displayed resistant to all conventional HCC therapies. Three potential therapeutic agents and four targets were further identified for high-PRS HCC patients.Our study generated a clinically valid molecular classification to guide precision medicine in patients with HCC.
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