Chen Ying, Yin Dian, Feng Xiu, He Shennan, Zhang Liang, Chen Dongqin
Department of Oncology, Nantong First People's Hospital and Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226000, People's Republic of China.
Cancer Manag Res. 2024 Dec 27;16:1793-1811. doi: 10.2147/CMAR.S482688. eCollection 2024.
The development and progression of Hepatocellular Carcinoma (HCC) is more relevant to immune regulation. Therefore, there is an urgent need to find immune-related molecular markers that can predict the prognosis and immune status of HCC.
RNA-seq and clinical HCC data from the Cancer Genome Atlas (TCGA) were analyzed for differential expression of microRNA (miRNAs), mRNAs, and lncRNAs. MiRNAs associated with immune scores were identified by Spearman analysis and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. MiRNAs and mRNAs were screened for prognosticity using COX regression. Kaplan-Meier survival analysis, risk scores, and correlation with clinical features were performed. Immune infiltration, Tumor Immune Dysfunction and Exclusion (TIDE), and chemotherapy prediction analyses were performed for high and low risk groups. Finally, prognostic mRNA expression was validated in cell lines.
Five prognostic miRNAs (hsa-miR-145-3p, hsa-miR-150-3p, hsa-miR-153-3p, hsa-miR-223-3p, hsa-miR-424-3p) were identified in the study. A risk score model based on these prognostic miRNAs accurately predicted overall survival and was validated in GSE31384. Six mRNAs (KCTD17, MAFG, RAB10, SFPQ, TRMT6, UBE2D2) were further identified as prognostic. A risk model including these mRNAs also accurately predicted overall survival, and higher risk scores were associated with lower survival. Univariate and multivariate Cox regression analyses confirmed that both miRNA and mRNA risk scores were independent prognostic factors. The TIDE results showed lower TIDE scores and T-cell exclusion scores in the low risk score group. Chemotherapeutic drug sensitivity analysis revealed that the high-risk group was more sensitive to multiple chemotherapeutic agents. In addition, real-time quantitative PCR (RT-qPCR) results of the cell lines supported the results of the public database analysis.
This study validated immune-related prognostic miRNAs and mRNAs and identified risk signatures for HCC, potentially advancing HCC prognosis and treatment.
肝细胞癌（HCC）的发生和进展与免疫调节更为相关。因此，迫切需要找到能够预测HCC预后和免疫状态的免疫相关分子标志物。
对来自癌症基因组图谱（TCGA）的RNA测序和临床HCC数据进行分析，以检测微小RNA（miRNA）、信使核糖核酸（mRNA）和长链非编码RNA（lncRNA）的差异表达。通过Spearman分析以及基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，确定与免疫评分相关的miRNA。使用COX回归筛选具有预后价值的miRNA和mRNA。进行Kaplan-Meier生存分析、风险评分以及与临床特征的相关性分析。对高风险组和低风险组进行免疫浸润、肿瘤免疫功能障碍和排除（TIDE）以及化疗预测分析。最后，在细胞系中验证预后mRNA的表达。
本研究确定了5种具有预后价值的miRNA（hsa-miR-145-3p、hsa-miR-150-3p、hsa-miR-153-3p、hsa-miR-223-3p、hsa-miR-424-3p）。基于这些具有预后价值的miRNA构建的风险评分模型能够准确预测总生存期，并在GSE31384中得到验证。进一步确定了6种具有预后价值的mRNA（KCTD17、MAFG、RAB10、SFPQ、TRMT6、UBE2D2）。包含这些mRNA的风险模型也能准确预测总生存期，且风险评分越高，生存期越低。单因素和多因素COX回归分析证实，miRNA和mRNA风险评分均为独立的预后因素。TIDE结果显示，低风险评分组的TIDE评分和T细胞排除评分较低。化疗药物敏感性分析表明，高风险组对多种化疗药物更敏感。此外，细胞系的实时定量聚合酶链反应（RT-qPCR）结果支持了公共数据库分析的结果。
本研究验证了与免疫相关的预后miRNA和mRNA，并确定了HCC的风险特征，可能推动HCC的预后和治疗进展。
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