Deng Jianxiong, Zhong Fangyan, Gu Weiguo, Qiu Feng
Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
Evol Bioinform Online. 2021 Feb 12;17:1176934321994109. doi: 10.1177/1176934321994109. eCollection 2021.
Hepatocellular carcinoma (HCC) is one of the common cancers with a high incidence and mortality. The human replication factor C (RFC) family contains 5 subunits that play an important role in DNA replication and DNA damage repair. RFCs are abnormally expressed in a variety of cancers; some of them are differentially expressed in HCC tissues and related to tumor growth. However, the expression, prognostic value, and effect targets of the whole RFC family in HCC are still unclear. To address these issues, we performed a multidimensional analysis of RFCs in HCC patients by Oncomine, UALCAN, GEPIA, Human protein atlas, Kaplan-Meier plotter, cBioPortal, GeneMANIA, String, and LinkedOmics. mRNA expression of RFCs was significantly increased in HCC tissues. There was a significant correlation between the expression of RFC2/3/4/5 and tumor stage of HCC patients. Besides, high mRNA expression of RFC2/4 was associated with worse overall survival (OS). Moreover, genetic alterations of RFCs were associated with worse OS in HCC patients. We found that genes co-expressed with RFC2/4 were mainly involved in biological processes, such as chromosome segregation, mitotic cell cycle phase transition, and telomere organization and they activated the cell cycle and spliceosome pathways. The gene set is mainly enriched in cancer-related kinases AURKA, ATR, CDK1, PLK1, and CHEK1. E2F family members were the key transcription factors for RFCs. Our results suggest that differentially expressed RFC2 and RFC4 are potential prognostic biomarkers in HCC and may act on E2F transcription factors and some kinase targets to dysregulate the cell cycle pathway. These efforts may provide new research directions for prognostic biomarkers and therapeutic targets in HCC.
肝细胞癌（HCC）是一种常见的癌症，发病率和死亡率都很高。人类复制因子C（RFC）家族包含5个亚基，在DNA复制和DNA损伤修复中起重要作用。RFCs在多种癌症中异常表达；其中一些在HCC组织中差异表达，并与肿瘤生长相关。然而，整个RFC家族在HCC中的表达、预后价值和作用靶点仍不清楚。为了解决这些问题，我们通过Oncomine、UALCAN、GEPIA、人类蛋白质图谱、Kaplan-Meier绘图仪、cBioPortal、GeneMANIA、String和LinkedOmics对HCC患者的RFCs进行了多维度分析。RFCs的mRNA表达在HCC组织中显著增加。RFC2/3/4/5的表达与HCC患者的肿瘤分期之间存在显著相关性。此外，RFC2/4的高mRNA表达与较差的总生存期（OS）相关。此外，RFCs的基因改变与HCC患者较差的OS相关。我们发现与RFC2/4共表达的基因主要参与染色体分离、有丝分裂细胞周期阶段转变和端粒组织等生物学过程，它们激活了细胞周期和剪接体途径。该基因集主要富集于与癌症相关的激酶AURKA、ATR、CDK1、PLK1和CHEK1。E2F家族成员是RFCs的关键转录因子。我们的结果表明，差异表达的RFC2和RFC4是HCC潜在的预后生物标志物，可能作用于E2F转录因子和一些激酶靶点，从而失调细胞周期途径。这些研究可能为HCC的预后生物标志物和治疗靶点提供新的研究方向。
