New HCC Subtypes Based on CD8 Tex-Related lncRNA Signature Could Predict Prognosis, Immunological and Drug Sensitivity Characteristics of Hepatocellular Carcinoma

作者：Jiachen Ge, Tao Ming, Gaolei Zhang, Jian‐Ping Cai, Deyu Li, Lianyuan Tao · 发表于：Journal of Hepatocellular Carcinoma · 年份：2024 · DOI：10.2147/jhc.s459150 · 被引用次数：10 · 研究领域：Cancer-related molecular mechanisms research、Ferroptosis and cancer prognosis、Cancer Immunotherapy and Biomarkers

Purpose: Hepatocellular carcinoma has become one of the severe diseases threatening human health. T cell exhaustion is deemed as a reason for immunotherapy resistance. However, little is known about the roles of CD8 Tex-related lncRNAs in HCC. Materials and Methods: We processed single-cell RNA sequencing to identify CD8 Tex-related genes. CD8 Tex-related lncRNAs were identified based on their correlations with mRNAs. Unsupervised clustering approach was used to identify molecular clusters of CD8 Tex-related lncRNAs. Differences in prognosis and immune infiltration between the clusters were explored. Machine learning algorithms were used to construct a prognostic signature. Samples were classified as low- and high-risk groups based on their risk scores. We identified prognosis-related lncRNAs and constructed a ceRNA network. In vitro experiments were conducted to investigate the impacts of CD8 Tex-related lncRNAs on proliferation and apoptosis of HCC cells. Results: We clarified cell types within two HCC single-cell datasets. We identified specific markers of CD8 Tex cells and analyzed their potential functions. Twenty-eight lncRNAs were identified as CD8 Tex-related. Based on CD8 Tex-related lncRNAs, samples were categorized into two distinct clusters, which exhibited significant differences in survival rates and immune infiltration. Ninety-six algorithm combinations were employed to establish a prognostic signature. RSF emerged as the one with the highest C-index. Patients ...