Research Papers:

Co-expression network analysis identified six hub genes in association with metastasis risk and prognosis in hepatocellular carcinoma

Pengfei Chen, Fan Wang, Juerong Feng, Rui Zhou, Ying Chang, Jing Liu and Qiu Zhao _

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Oncotarget. 2017; 8:48948-48958. https://doi.org/10.18632/oncotarget.16896

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Pengfei Chen1,2,3,*, Fan Wang1,2,*, Juerong Feng1,2, Rui Zhou1,2, Ying Chang1,2, Jing Liu1,2 and Qiu Zhao1,2

1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China

2Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China

3Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China

*These authors contributed equally to this work

Correspondence to:

Qiu Zhao, email: [email protected]

Keywords: hepatocellular carcinoma, co-expression network analysis, hub genes, metastasis risk, prognosis

Received: January 31, 2017     Accepted: March 21, 2017     Published: April 06, 2017


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.

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