Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing 210029, China.
Medicina (Kaunas). 2023 Sep 18;59(9):1682. doi: 10.3390/medicina59091682.
The modification of histone acetylation plays a vital role in regulating tumor occurrence and development, but the interaction between histone acetylation modulator genes and the liver hepatocellular carcinoma (LIHC) microenvironment, as well as immunotherapy, has not been investigated. Analysis of all statistical data was carried out using R software (Version 4.2.0) and the online tool Sangerbox. Comprehensive bioinformatics analysis, including signature construction and validation, functional analyses, immune and genomic features analyses, and immunotherapy prediction analyses, were performed to explore the prognostic and therapeutic role of histone acetylation modulator genes in LIHC development and progression. The LIHC cohort from The Cancer Genome Atlas (TCGA) database was selected as the training cohort; the GSE76427 cohort from the Gene Expression Omnibus (GEO) database and the LIRI-JP cohort from the International Cancer Genome Consortium (ICGC) database were selected as the validation cohorts. The histone acetylation modulator gene-based prognostic signature was constructed and validated successfully. Immune infiltration analysis showed that most immune cells and immune functions were enriched in patients with high histone acetylation risk scores (HARS). Additionally, high levels of checkpoint inhibitors (ICIs) and human leukocyte antigens (HLAs) were also observed in high HARS patients. Meanwhile, TIDE algorithm analysis was conducted to explore the relationship between HARS and immunotherapy response, and submap algorithm analysis was used for the verification of the results, from which we found that high HAPS patients were more likely to respond to immunotherapy. Our findings revealed that the histone acetylation modulator genes, particularly for KAT21, SIRT6, and HAT1, may have the potential to function as a new prognostic marker and therapeutic target for LIHC.
组蛋白乙酰化修饰在调控肿瘤发生发展中起着至关重要的作用，但组蛋白乙酰化修饰酶基因与肝癌（LIHC）微环境以及免疫治疗之间的相互作用尚未得到研究。所有统计数据的分析均使用 R 软件（版本 4.2.0）和在线工具 Sangerbox 进行。通过综合生物信息学分析，包括特征构建和验证、功能分析、免疫和基因组特征分析以及免疫治疗预测分析，探讨了组蛋白乙酰化修饰酶基因在 LIHC 发展和进展中的预后和治疗作用。从癌症基因组图谱（TCGA）数据库中选择 LIHC 队列作为训练队列；从基因表达综合数据库（GEO）中选择 GSE76427 队列，从国际癌症基因组联合会（ICGC）中选择 LIRI-JP 队列作为验证队列。成功构建和验证了基于组蛋白乙酰化修饰酶基因的预后特征。免疫浸润分析表明，大多数免疫细胞和免疫功能在高组蛋白乙酰化风险评分（HARS）患者中富集。此外，在高 HARS 患者中还观察到高水平的检查点抑制剂（ICIs）和人类白细胞抗原（HLAs）。同时，还进行了 TIDE 算法分析以探讨 HARS 与免疫治疗反应之间的关系，并使用子图算法进行了结果验证，从中我们发现高 HARS 患者更有可能对免疫治疗产生反应。我们的研究结果表明，组蛋白乙酰化修饰酶基因，特别是 KAT21、SIRT6 和 HAT1，可能具有作为 LIHC 新的预后标志物和治疗靶点的潜力。
