College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Curr Gene Ther. 2025;25(2):178-193. doi: 10.2174/0115665232298240240529131358.
Investigating the impact of stemness-related circadian rhythm disruption (SCRD) on hepatocellular carcinoma (HCC) prognosis and its potential as a predictor for immunotherapy response.
Circadian disruption has been linked to tumor progression through its effect on the stemness of cancer cells.
Develop a novel signature for SCRD to accurately predict clinical outcomes and immune therapy response in patients with HCC.
The stemness degree of patients with HCC was assessed based on the stemness index (mRNAsi). The co-expression circadian genes significantly correlated with mRNAsi were identified and defined as stemness- and circadian-related genes (SCRGs). The SCRD scores of samples and cells were calculated based on the SCRGs. Differentially expressed genes with a prognostic value between distinct SCRD groups were identified in bulk and single-cell datasets to develop an SCRD signature.
A higher SCRD score indicates a worse patient survival rate. Analysis of the tumor microenvironment revealed a significant correlation between SCRD and infiltrating immune cells. Heterogeneous expression patterns, functional states, genomic variants, and cell-cell interactions between two SCRD populations were revealed by transcriptomic, genomic, and interaction analyses. The robust SCRD signature for predicting immunotherapy response and prognosis in patients with HCC was developed and validated in multiple independent cohorts.
In summary, distinct tumor immune microenvironment patterns were confirmed under SCRD in bulk and single-cell transcriptomic, and SCRD signature associated with clinical outcomes and immunotherapy response was developed and validated in HCC.
研究与干细胞相关的昼夜节律紊乱（SCRD）对肝细胞癌（HCC）预后的影响及其作为免疫治疗反应预测因子的潜力。
昼夜节律紊乱通过对癌细胞的干细胞特性的影响与肿瘤进展有关。
开发一种新的 SCRD 特征，以准确预测 HCC 患者的临床结局和免疫治疗反应。
根据干细胞指数（mRNAsi）评估 HCC 患者的干细胞程度。确定与 mRNAsi 显著相关的共表达昼夜节律基因，并将其定义为与干细胞和昼夜节律相关的基因（SCRGs）。根据 SCRGs 计算样本和细胞的 SCRD 评分。在批量和单细胞数据集之间鉴定具有不同 SCRD 组之间预后价值的差异表达基因，以开发 SCRD 特征。
较高的 SCRD 评分表明患者的生存率较低。肿瘤微环境分析表明 SCRD 与浸润免疫细胞之间存在显著相关性。通过转录组、基因组和相互作用分析揭示了两个 SCRD 群体之间的异质表达模式、功能状态、基因组变异和细胞间相互作用。在多个独立队列中开发和验证了用于预测 HCC 患者免疫治疗反应和预后的稳健 SCRD 特征。
总之，在批量和单细胞转录组中证实了 SCRD 下不同的肿瘤免疫微环境模式，并开发和验证了与临床结局和免疫治疗反应相关的 SCRD 特征。
