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目的 分析端粒酶逆转录酶（TERT）在肝细胞肝癌中的表达及其与预后和免疫细胞浸润的关系。方法 通过癌症基因组图谱-肝细胞癌（TCGA-LIHC）和GSE124535数据集，分析TERT在肝细胞肝癌中的表达水平及其与肝细胞肝癌患者预后的关系。采用基因集富集分析（GSEA）识别与TERT相关的生物学途径。利用单样本基因集富集分析（ssGSEA）算法评估免疫细胞浸润，并分析TERT表达与免疫细胞浸润的关系。结果 在TCGA数据库和GSE124535数据集中，TERT在肝细胞肝癌肿瘤组织中的表达显著高于癌旁组织（均P<0.001）。在TCGA数据库中，TERT高表达肝细胞肝癌患者显示出较差的总生存时间（P=0.037）和无进展间隔时间（P=0.006）。在GSE124535数据集中，TERT高表达肝细胞肝癌患者的无病生存时间较差（P=0.190）。GSEA结果显示，端粒维持和细胞周期通路在TERT高表达组中显著富集。ssGSEA结果显示，TERT高表达组中CD8+T细胞、树突状细胞和自然杀伤细胞浸润水平较低，2型辅助T细胞浸润水平较高（均P<0.05）。结论 TERT高表达可能通过促进肝细胞肝癌增殖和抑制免疫细胞浸润导致肝细胞肝癌患者的不良预后。TERT可作为预测肝细胞肝癌患者预后和免疫浸润水平的潜在生物标志物。
Abstract：Objective To analyze the expression of telomerase reverse transcriptase(TERT in hepatocellular carcinoma(HCC) and its relationship with prognosis and immune infiltration.Methods The expression of TERT and its association with the prognosis of patients with HCC were analyzed using The Cancer Genome Atlas-liver hepatocellular carcinoma(TCGA-LIHC) and GSE124535dataset. Gene set enrichment analysis(GSEA) was performed to identify TERT-related biological pathways. Single-sample gene set enrichment analysis(ssGSEA) was used to evaluate scores of immune cell infiltration, and the relationship between the expression of TERT and immune cell infiltration was explored. Results In TCGA and GSE124535 datasets, the expression of TERT was significantly higher in tumor tissues compared to adjacent non-tumor tissues(all P<0.001). In TCGA database, patients with higher TERT expression showed poorer overall survival(P=0.037) and progression-free interval(P=0.006) than those with lower TERT expression. In GSE124535 dataset, patients with higher TERT expression showed poorer disease-free survival(P=0.190). GSEA results indicated that telomere maintenance and cell cycle pathways were significantly enriched in high TERT expression group. ss GSEA results revealed that the high TERT expression group displayed decreased infiltration scores of CD8+ T cells, dendritic cells, and natural killer cells, and exhibited elevated infiltration score of type 2 helper T cells(all P<0.05). Conclusions High TERT expression may lead to poor prognosis in patients with HCC by promoting HCC proliferation and suppressing immune cell infiltration. TERT could serve as a potential biomarker for predicting prognosis and immune infiltration of patients with HCC.
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基本信息:
DOI：10.13455/j.cnki.cjcor.113494-20230805-0126
中图分类号:R735.7
引用信息:
[1]郑琳琳,刘振荣,李海洋,等.端粒酶逆转录酶在肝细胞肝癌中的表达及其与预后和免疫细胞浸润的关系[J].中国肿瘤临床与康复,2023,30(08):499-506.DOI:10.13455/j.cnki.cjcor.113494-20230805-0126.
基金信息:
中国癌症基金会北京希望马拉松专项基金（LC2020L05）~~
2023-11-28
2023-11-28