Identification of Flap endonuclease 1 as a potential core gene in hepatocellular carcinoma by integrated bioinformatics analysis

Chuanfei Li; Feng Qin; Hao Hong; Hui Tang; Xiaoling Jiang; Shuangyan Yang; Zhechuan Mei; Di Zhou

doi:10.7717/peerj.7619

Identification of Flap endonuclease 1 as a potential core gene in hepatocellular carcinoma by integrated bioinformatics analysis

PeerJ. 2019 Sep 6:7:e7619. doi: 10.7717/peerj.7619. eCollection 2019.

Authors

Chuanfei Li¹, Feng Qin², Hao Hong³, Hui Tang⁴, Xiaoling Jiang⁵, Shuangyan Yang⁴, Zhechuan Mei¹, Di Zhou⁶

Affiliations

¹ Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² Department of Infectious Diseases, The People's Hospital of Shi Zhu, Chongqing, China.
³ Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
⁴ Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
⁵ Tongnan District People's Hospital, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
⁶ Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Abstract

Hepatocellular carcinoma (HCC) is a common yet deadly form of malignant cancer. However, the specific mechanisms involved in HCC diagnosis have not yet fully elucidated. Herein, we screened four publically available Gene Expression Omnibus (GEO) expression profiles (GSE14520, GSE29721, GSE45267 and GSE60502), and used them to identify 409 differentially expressed genes (DEGs), including 142 and 267 up- and down-regulated genes, respectively. The DAVID database was used to look for functionally enriched pathways among DEGs, and the STRING database and Cytoscape platform were used to generate a protein-protein interaction (PPI) network for these DEGs. The cytoHubba plug-in was utilized to detect 185 hub genes, and three key clustering modules were constructed with the MCODE plug-in. Gene functional enrichment analyses of these three key clustering modules were further performed, and nine core genes including BIRC5, DLGAP5, DTL, FEN1, KIAA0101, KIF4A, MCM2, MKI67, and RFC4, were identified in the most critical cluster. Subsequently, the hierarchical clustering and expression of core genes in TCGA liver cancer tissues were analyzed using the UCSC Cancer Genomics Browser, and whether elevated core gene expression was linked to a poor prognosis in HCC patients was assessed using the GEPIA database. The PPI of the nine core genes revealed an interaction between FEN1, MCM2, RFC4, and BIRC5. Furthermore, the expression of FEN1 was positively correlated with that of three other core genes in TCGA liver cancer tissues. FEN1 expression in HCC and other tumor types was assessed with the FIREBROWSE and ONCOMINE databases, and results were verified in HCC samples and hepatoma cells. FEN1 levels were also positively correlated with tumor size, distant metastasis and vascular invasion. In conclusion, we identified nine core genes associated with HCC development, offering novel insight into HCC progression. In particular, the aberrantly elevated FEN1 may represent a potential biomarker for HCC diagnosis and treatment.

Keywords: Bioinformatics analysis; Core genes; Flap endonuclease 1; Hepatocellular carcinoma.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81300258, 81801717) and the Medical Science Cultivation Fund of the First Affiliated Hospital of Chongqing Medical University (PYJJ2018-15). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.