Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Division of Gastrointestinal Surgery, Department of General Surgery, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an Second People's Hospital, Huai'an, China.
Funct Integr Genomics. 2023 Apr 18;23(2):128. doi: 10.1007/s10142-023-01060-w.
Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence worldwide. The underlying mechanisms remain poorly understood. The DNA metabolic process of homologous recombination repair (HRR) has been linked to a high probability of tumorigenesis and drug resistance. This study aimed to determine the role of HRR in HCC and identify critical HRR-related genes that affect tumorigenesis and prognosis. A total of 613 tumor and 252 para-carcinoma tissue samples were collected from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) to obtain differentially expressed genes (DEGs). HRR-related genes were assessed using gene enrichment and pathway analyses. Survival analysis was performed using the Kaplan-Meier method in the Gene Expression Profiling Interactive Analysis portal. The levels of RAD54L in the HRR pathway were detected by RT-qPCR and western blotting in para-carcinoma and HCC tissues and in L02 normal human liver cells and Huh7 HCC cells. Immunohistochemistry (IHC) was performed on the clinical specimens to determine the connection between gene expression and clinical features. Bioinformatics analysis revealed that the HRR pathway was enriched in HCC tissues. Upregulation of HRR pathway DEGs in HCC tissues was positively correlated with tumor pathological staging and negatively associated with patient overall survival. RAD54B, RAD54L, and EME1 genes in the HRR pathway were screened as markers for predicting HCC prognosis. RT-qPCR identified RAD54L as the most significantly expressed of the three genes. Western blotting and IHC quantitative analyses further demonstrated that RAD54L protein levels were higher in HCC tissues. IHC analysis of 39 pairs of HCC and para-carcinoma tissue samples also revealed an association between RAD54L and Edmondson-Steiner grade and the proliferation-related gene Ki67. The collective findings positively correlate RAD54L in the HRR signaling pathway with HCC staging and implicate RAD54L as a marker to predict HCC progression.
肝细胞癌 (HCC) 是一种在全球范围内发病率较高的恶性肿瘤。其潜在机制仍知之甚少。同源重组修复 (HRR) 的 DNA 代谢过程与肿瘤发生和耐药性的高概率相关。本研究旨在确定 HRR 在 HCC 中的作用，并确定影响肿瘤发生和预后的关键 HRR 相关基因。从癌症基因组图谱 (TCGA) 和国际癌症基因组联盟 (ICGC) 共收集了 613 例肿瘤和 252 例癌旁组织样本，以获得差异表达基因 (DEGs)。使用基因富集和途径分析评估 HRR 相关基因。使用基因表达谱交互式分析门户中的 Kaplan-Meier 方法进行生存分析。通过 RT-qPCR 和 Western blot 在癌旁和 HCC 组织以及 L02 正常人类肝细胞和 Huh7 HCC 细胞中检测 HRR 通路中的 RAD54L 水平。对临床标本进行免疫组织化学 (IHC) 检测以确定基因表达与临床特征之间的关系。生物信息学分析显示 HRR 途径在 HCC 组织中富集。HCC 组织中 HRR 途径 DEGs 的上调与肿瘤病理分期呈正相关，与患者总生存呈负相关。筛选 HRR 途径中的 RAD54B、RAD54L 和 EME1 基因作为预测 HCC 预后的标志物。RT-qPCR 确定 RAD54L 为这三个基因中表达最显著的基因。Western blot 和 IHC 定量分析进一步表明，RAD54L 蛋白水平在 HCC 组织中较高。对 39 对 HCC 和癌旁组织样本的 IHC 分析也表明 RAD54L 与 Edmondson-Steiner 分级和与增殖相关的基因 Ki67 之间存在关联。综上所述，HRR 信号通路中的 RAD54L 与 HCC 分期呈正相关，并提示 RAD54L 可作为预测 HCC 进展的标志物。
