Abstract
Hepatocellular carcinoma (HCC) has a high incidence and mortality worldwide, and its carcinogenesis and progression are influenced by a complex network of gene interactions. A weighted gene co-expression network was constructed to identify gene modules associated with the clinical traits in HCC (n = 214). Among the 13 modules, high correlation was only found between the red module and metastasis risk (classified by the HCC metastasis gene signature) (R2 = −0.74). Moreover, in the red module, 34 network hub genes for metastasis risk were identified, six of which (ABAT, AGXT, ALDH6A1, CYP4A11, DAO and EHHADH) were also hub nodes in the protein-protein interaction network of the module genes. Thus, a total of six hub genes were identified. In validation, all hub genes showed a negative correlation with the four-stage HCC progression (P for trend < 0.05) in the test set. Furthermore, in the training set, HCC samples with any hub gene lowly expressed demonstrated a higher recurrence rate and poorer survival rate (hazard ratios with 95% confidence intervals > 1). RNA-sequencing data of 142 HCC samples showed consistent results in the prognosis. Gene set enrichment analysis (GSEA) demonstrated that in the samples with any hub gene highly expressed, a total of 24 functional gene sets were enriched, most of which focused on amino acid metabolism and oxidation. In conclusion, co-expression network analysis identified six hub genes in association with HCC metastasis risk and prognosis, which might improve the prognosis by influencing amino acid metabolism and oxidation.
Highlights
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it is the second leading cause of cancer-related death among males [1]
The samples had an average age of 50.7 years, and a high proportion of males (86.4%, 185/214) (Figure 1). 87 (40.7%) cases had high levels of serum alanine aminotransferase (ALT, > 50 U/L), and 97 (45.3%) with high levels of serum alpha-fetoprotein (AFP, > 300 ng/ml). 197 (92.1%) cases were concomitant with cirrhosis. 44 (20.6%) cases were multinodular, and the main tumor size in 77 (36.0%) cases were more than 5 cm
Hepatocellular carcinoma is the most frequent malignant tumor in the liver, and its mortality is high which contributes to the high frequency of late-stage disease, metastasis and the “field effect” [6]
Summary
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and it is the second leading cause of cancer-related death among males [1]. Multiple factors were reported to be related with the carcinogenesis and progression in HCC, like chronic infection of hepatitis B virus (HBV) or hepatitis C virus (HCV), alcohol consumption and smoking [2]. With the development of gene microarray and RNA sequencing, gene expression profiling has been used to identify genes associated the carcinogenesis and development of HCC. Most studies focused on the screening of differentially expressed genes, and ignored the high interconnection between genes genes with similar expression patterns are probably correlated in function [3]. We adopted the systems biologybased approach of weighted gene co-expression network analysis (WGCNA) to construct a co-expression network based on the relationship between genes, and identified significant gene modules and hub genes associated with the clinical traits in HCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
