Department of Radiation Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, China.
Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University Medical School, Hangzhou 310016, China.
Oxid Med Cell Longev. 2023 Jan 20;2023:3878796. doi: 10.1155/2023/3878796. eCollection 2023.
Ribonucleotide reductase (RR) consists of two subunits, the large subunit RRM1 and the small subunit (RRM2 or RRM2B), which is essential for DNA replication. Dysregulations of RR were implicated in multiple types of cancer. However, the abnormal expressions and biologic functions of RR subunits in liver cancer remain to be elucidated.
TCGA, HCCDB, CCLE, HPA, cBioPortal, and GeneMANIA were utilized to perform bioinformatics analysis of RR subunits in the liver cancer. GO, KEGG, and GSEA were used for enrichment analysis.
The expressions of RRM1, RRM2, and RRM2B were remarkably upregulated among liver cancer tissue both in mRNA and protein levels. High expression of RRM1 and RRM2 was notably associated with high tumor grade, high stage, short overall survival, and disease-specific survival. Enrichment analyses indicated that RRM1 and RRM2 were related to DNA replication, cell cycle, regulation of nuclear division, DNA repair, and DNA recombination. Correlation analysis indicated that RRM1 and RRM2 were significantly associated with several subsets of immune cell, including Th2 cells, cytotoxic cells, and neutrophils. RRM2B expression was positively associated with immune score and stromal score. Chemosensitivity analysis revealed that sensitivity of nelarabine was positively associated with high expressions of RRM1 and RRM2. The sensitivity of rapamycin was positively associated with high expressions of RRM2B.
Our findings demonstrated high expression profiles of RR subunits in liver cancer, which may provide novel insights for predicting the poor prognosis and increased chemosensitivity of liver cancer in clinic.
核苷酸还原酶（RR）由两个亚基组成，大亚基 RRM1 和小亚基（RRM2 或 RRM2B），这对于 DNA 复制是必不可少的。RR 的失调与多种类型的癌症有关。然而，肝癌中 RR 亚基的异常表达和生物学功能仍有待阐明。
利用 TCGA、HCCDB、CCLE、HPA、cBioPortal 和 GeneMANIA 对肝癌中 RR 亚基进行生物信息学分析。GO、KEGG 和 GSEA 用于富集分析。
RRM1、RRM2 和 RRM2B 在肝癌组织中的 mRNA 和蛋白水平均显著上调。RRM1 和 RRM2 的高表达与高肿瘤分级、高分期、总生存期和疾病特异性生存期短显著相关。富集分析表明，RRM1 和 RRM2 与 DNA 复制、细胞周期、核分裂调节、DNA 修复和 DNA 重组有关。相关性分析表明，RRM1 和 RRM2 与包括 Th2 细胞、细胞毒性细胞和嗜中性粒细胞在内的几种免疫细胞亚群显著相关。RRM2B 的表达与免疫评分和基质评分呈正相关。化疗敏感性分析表明，奈拉滨的敏感性与 RRM1 和 RRM2 的高表达呈正相关。雷帕霉素的敏感性与 RRM2B 的高表达呈正相关。
我们的研究结果表明 RR 亚基在肝癌中呈现高表达谱，这可能为预测肝癌的不良预后和增加化疗敏感性提供新的思路。
