Zhang Yuan, Chen Xiaorong, Cao Yajuan, Yang Zongguo
Department of Integrative Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People's Republic of China.
Clinical Translation Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People's Republic of China.
Cancer Manag Res. 2021 Apr 22;13:3503-3515. doi: 10.2147/CMAR.S302917. eCollection 2021.
The role of the complement and coagulation cascades signaling pathway in the pathogenesis of cancers remains uncertain. This study aimed to investigate the associations between enriched differentially expressed genes (DEGs) in this pathway and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients.
Clinical and gene expression data of the Gene Expression Omnibus (GEO) series profile GSE14520 were downloaded. The "Limma" package was used to screen the DEGs and the "clusterProfiler" package was used to identify the complement and coagulation cascades pathway and enriched significant genes. Cox regression analysis, the Kaplan-Meier method, and the nomogram model were used to address the correlations between significantly enriched DEGs in the complement and coagulation cascades pathway and HCC survival.
A total of 220 HBV-related HCC patients were enrolled in this study. The complement and coagulation cascades pathway was significantly enriched by 37 DEGs (p-value < 0.05 and adjusted p-value < 0.05). Complement 8 beta chain (C8B) expression levels had protective effects on overall survival (OS) and recurrence-free survival (RFS) in HBV-related HCC patients. High levels of C8B contributed to favorable OS and RFS in this population (both p < 0.01), even after adjustment of clinicopathological characteristics including tumor node metastasis (TNM) staging, Barcelona Clinic liver cancer (BCLC) staging, gender, and fibrinogen beta chain (FGB) expression (all p < 0.05).
C8B in the complement and coagulation cascades signaling pathway serves as a predictive candidate for survival in HBV-related HCC patients.
补体和凝血级联信号通路在癌症发病机制中的作用仍不明确。本研究旨在探讨该通路中富集的差异表达基因(DEGs)与乙型肝炎病毒(HBV)相关肝细胞癌(HCC)患者之间的关联。
下载基因表达综合数据库(GEO)系列谱GSE14520的临床和基因表达数据。使用“Limma”软件包筛选DEGs,使用“clusterProfiler”软件包鉴定补体和凝血级联通路及富集的显著基因。采用Cox回归分析、Kaplan-Meier法和列线图模型来分析补体和凝血级联通路中显著富集的DEGs与HCC患者生存之间的相关性。
本研究共纳入220例HBV相关HCC患者。补体和凝血级联通路被37个DEGs显著富集(p值<0.05且校正p值<0.05)。补体8β链(C8B)表达水平对HBV相关HCC患者的总生存期(OS)和无复发生存期(RFS)具有保护作用。即使在调整了包括肿瘤淋巴结转移(TNM)分期、巴塞罗那临床肝癌(BCLC)分期、性别和纤维蛋白原β链(FGB)表达等临床病理特征后,高水平的C8B仍有助于该人群获得良好的OS和RFS(均p<0.05)。
补体和凝血级联信号通路中的C8B可作为HBV相关HCC患者生存的预测指标。