Bioinformatics analysis to identify the key genes affecting the progression and prognosis of hepatocellular carcinoma.

Yingai Zhang,Jingchuan Xiao,Shunlan Wang,Hailong Zhou

doi:10.1042/bsr20181845

Yingai Zhang, Jingchuan Xiao + Show 2 more

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https://doi.org/10.1042/bsr20181845

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Journal: Bioscience reports	Publication Date: Feb 22, 2019
Citations: 6	License type: CC BY 4.0

Affiliation: Hainan University, Central South University

Abstract

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, which has poor outcome. The present study aimed to investigate the key genes implicated in the progression and prognosis of HCC. The RNA-sequencing data of HCC was extracted from The Cancer Genome Atlas (TCGA) database. Using the R package (DESeq), the differentially expressed genes (DEGs) were analyzed. Based on the Cluepedia plug-in in Cytoscape software, enrichment analysis for the protein-coding genes amongst the DEGs was conducted. Subsequently, protein–protein interaction (PPI) network was built by Cytoscape software. Using survival package, the genes that could distinguish the survival differences of the HCC samples were explored. Moreover, quantitative real-time reverse transcription-PCR (qRT-PCR) experiments were used to detect the expression of key genes. There were 2193 DEGs in HCC samples. For the protein-coding genes amongst the DEGs, multiple functional terms and pathways were enriched. In the PPI network, cyclin-dependent kinase 1 (CDK1), polo-like kinase 1 (PLK1), Fos proto-oncogene, AP-1 transcription factor subunit (FOS), serum amyloid A1 (SAA1), and lysophosphatidic acid receptor 3 (LPAR3) were hub nodes. CDK1 interacting with PLK1 and FOS, and LPAR3 interacting with FOS and SAA1 were found in the PPI network. Amongst the 40 network modules, 4 modules were with scores not less than 10. Survival analysis showed that anterior gradient 2 (AGR2) and RLN3 could differentiate the high- and low-risk groups, which were confirmed by qRT-PCR. CDK1, PLK1, FOS, SAA1, and LPAR3 might be key genes affecting the progression of HCC. Besides, AGR2 and RLN3 might be implicated in the prognosis of HCC.

Highlights

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and causes the most deaths in cirrhosis patients [1]
HCC usually occurs in people with chronic liver inflammation, which is closely related to virus infection or alcohol and aflatoxin exposure [2]
Epidemiological data show that the main risk factors for HCC are as follows: (i) Hepatitis B or hepatitis C virus infection. (ii) Aflatoxin. (iii) Drinking wastewater or pond water containing a large amount of organochlorine compounds and algae toxins. (iv) Other factors such as family aggregation, selenium deficiency, alcoholic and nutritional cirrhosis [2,3]

Summary

Introduction

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and causes the most deaths in cirrhosis patients [1]. HCC usually occurs in people with chronic liver inflammation, which is closely related to virus infection or alcohol and aflatoxin exposure [2]. Epidemiological data show that the main risk factors for HCC are as follows: (i) Hepatitis B or hepatitis C virus infection. The therapeutic schedules of HCC depend on disease stage, operative tolerance, and possibility of liver transplant [3,4]. The outcome of HCC patients is usually poor, because 80–90% HCCs cannot be resected completely and leads to death in 3–6 months [5,6]. HCC is amongst the most common tumors and results in more than 670000 deaths per year globally [7]. The mechanisms of HCC needed to be explored to improve its therapies

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