Huang Rui, Liu Jinying, Li Hui, Zheng Lierui, Jin Haojun, Zhang Yaqing, Ma Wei, Su Junhong, Wang Min, Yang Kun
College of Medicine, Northwest Minzu University, Lanzhou, China.
Lanzhou Maternity and Child Health Care Hospital, Lanzhou, China.
Front Genet. 2021 Apr 30;12:647353. doi: 10.3389/fgene.2021.647353. eCollection 2021.
Hepatocellular carcinoma (HCC) is a primary liver cancer with extremely high mortality in worldwide. HCC is hard to diagnose and has a poor prognosis due to the less understanding of the molecular pathological mechanisms and the regulation mechanism on immune cell infiltration during hepatocarcinogenesis. Herein, by performing multiple bioinformatics analysis methods, including the RobustRankAggreg (RRA) rank analysis, weighted gene co-expression network analysis (WGCNA), and a devolution algorithm (CIBERSORT), we first identified 14 hub genes (NDC80, DLGAP5, BUB1B, KIF20A, KIF2C, KIF11, NCAPG, NUSAP1, PBK, ASPM, FOXM1, TPX2, UBE2C, and PRC1) in HCC, whose expression levels were significantly up-regulated and negatively correlated with overall survival time. Moreover, we found that the expression of these hub genes was significantly positively correlated with immune infiltration cells, including regulatory T cells (Treg), T follicular helper (TFH) cells, macrophages M0, but negatively correlated with immune infiltration cells including monocytes. Among these hub genes, KIF2C and UBE2C showed the most significant correlation and were associated with immune cell infiltration in HCC, which was speculated as the potential prognostic biomarker for guiding immunotherapy.
肝细胞癌(HCC)是一种在全球范围内死亡率极高的原发性肝癌。由于对肝癌发生过程中的分子病理机制以及免疫细胞浸润的调控机制了解较少,HCC难以诊断且预后较差。在此,通过运用多种生物信息学分析方法,包括稳健排序聚合(RRA)排序分析、加权基因共表达网络分析(WGCNA)以及一种反卷积算法(CIBERSORT),我们首次在HCC中鉴定出14个核心基因(NDC80、DLGAP5、BUB1B、KIF20A、KIF2C、KIF11、NCAPG、NUSAP1、PBK、ASPM、FOXM1、TPX2、UBE2C和PRC1),这些基因的表达水平显著上调且与总生存时间呈负相关。此外,我们发现这些核心基因的表达与免疫浸润细胞显著正相关,包括调节性T细胞(Treg)、滤泡辅助性T细胞(TFH)、M0巨噬细胞,但与包括单核细胞在内的免疫浸润细胞呈负相关。在这些核心基因中,KIF2C和UBE2C显示出最显著的相关性,并与HCC中的免疫细胞浸润相关,推测其为指导免疫治疗的潜在预后生物标志物。