Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
J Surg Res. 2024 Oct;302:250-258. doi: 10.1016/j.jss.2024.07.046. Epub 2024 Aug 6.
RAD51 is a pivotal DNA repair gene managing double-stranded DNA break recognition and repair. RAD51 high expression was associated with adverse outcomes in other cancer types. This study aims to investigate the tumor microenvironment and immune landscape in the RAD51 high-expressed Hepatocellular Carcinoma (HCCs).
A total of 467 patients from two large independent cohorts with clinical and transcriptomic data were obtained. The cohort was dichotomized based on the median RAD51 gene expression. xCell and Gene Set Enrichment Analysis (GSEA) were used.
RAD51 high-expressed HCCs were associated with worse recurrence-free, progression-free, disease-specific, and overall survival (all P < 0.05). While RAD51 high-expressed HCCs were associated with intratumoral heterogeneity, homologous recombination deficiency, and fraction altered scores, mutation or neoantigens were not increased in this group. xCell analysis demonstrated inconsistent immune cell infiltration between two cohorts. Cytolytic activity as well as GSEA with immune-related gene sets also demonstrated inconsistent results between two cohorts as well. On the other hand, RAD51 expression was significantly increased in higher-grade tumors, larger tumors, and higher clinical stages. RAD51 high-expressed HCCs were found to have elevated proliferation score. Furthermore, GSEA exhibited significant enrichment of all the cell proliferation-related gene sets in the Hallmark collection, including E2F targets, G2M checkpoint, Mitotic spindle, MYC targets, and MTORC1 signaling consistently in both cohorts (all false discovery rate < 0.25).
RAD51 high-expressed HCCs were associated with worse survival and with increased cell proliferation and were not necessarily associated with immune infiltration or inflammation.
RAD51 是一种关键的 DNA 修复基因，负责双链 DNA 断裂的识别和修复。RAD51 高表达与其他癌症类型的不良预后相关。本研究旨在探讨 RAD51 高表达肝癌（HCCs）的肿瘤微环境和免疫景观。
共获得来自两个具有临床和转录组学数据的大型独立队列的 467 名患者。根据 RAD51 基因表达的中位数将队列分为两组。使用 xCell 和基因集富集分析（GSEA）。
RAD51 高表达 HCC 与无复发生存、无进展生存、疾病特异性生存和总生存较差相关（均 P<0.05）。虽然 RAD51 高表达 HCC 与肿瘤内异质性、同源重组缺陷和分数改变评分相关，但该组的突变或新抗原并未增加。xCell 分析表明两个队列之间免疫细胞浸润不一致。细胞溶解活性以及与免疫相关基因集的 GSEA 也在两个队列中得出不一致的结果。另一方面，RAD51 表达在高级别肿瘤、较大肿瘤和较高临床分期中显著增加。发现 RAD51 高表达 HCC 的增殖评分升高。此外，GSEA 在两个队列中均一致显示，所有与细胞增殖相关的基因集在 Hallmark 集合中均显著富集，包括 E2F 靶标、G2M 检查点、有丝分裂纺锤体、MYC 靶标和 MTORC1 信号（均错误发现率<0.25）。
RAD51 高表达 HCC 与生存较差相关，与细胞增殖增加相关，与免疫浸润或炎症不一定相关。
