Abstract

Objective The analysis of the gene expression of peripheral blood mononuclear cells (PBMCs) is important to clarify the pathogenesis of hepatocellular carcinoma (HCC) and the detection of suitable biomarkers. The purpose of this investigation was to use RNA-sequencing to screen the appropriate differentially expressed genes (DEGs) in the PBMCs for the HCC. Methods The comprehensive transcriptome of extracted RNA of PBMC (n = 20) from patients with chronic hepatitis B (CHB), liver cirrhosis, and early stage of HCC (5 samples per group) was carried out using RNA-sequencing. All raw RNA-sequencing data analyses were performed using conventional RNA-sequencing analysis tools. Next, gene ontology (GO) analyses were carried out to elucidate the biological processes of DEGs. Finally, relative transcript abundance of selected DEGs was verified using qRT-PCR on additional validation groups. Results Specifically, 13, 1262, and 1450 DEGs were identified for CHB, liver cirrhosis, and HCC, when compared with the healthy controls. GO enrichment analysis indicated that HCC is closely related to the immune response. Seven DEGs (TYMP, TYROBP, CD14, TGFBI, LILRA2, GNLY, and GZMB) were common to HCC, cirrhosis, and CHB when compared to healthy controls. The data revealed that the expressions of these 7 DEGs were consistent with those from the RNA-sequencing results. Also, the expressions of 7 representative genes that had higher sensitivity were obtained by receiver operating characteristic analysis, which indicated their important diagnostic accuracy for HBV-HCC. Conclusion This study provides us with new horizons into the biological process and potential prospective clinical diagnosis and prognosis of HCC in the near future.

Highlights

  • Hepatitis B virus (HBV) infection is the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide with an annual mortality rate of 1 million deaths

  • In terms of HBV viral loads, significant associations were found between patients in terms of HBV viral loads (P value

  • We found that these genes were involved in the immune response, which was shared by chronic hepatitis B infection (CHB), cirrhosis, and HCC, demonstrating that these 7 genes had potential values to diagnose HCC. ereafter, quantitative real-time PCR (qRT-PCR) was used for extra verification of these 7 genes

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Summary

Introduction

Hepatitis B virus (HBV) infection is the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide with an annual mortality rate of 1 million deaths. 50% of patients with chronic hepatitis B infection (CHB) will progress to liver cirrhosis and the annual incidence rate of HCC in this group is 4% [1]. Chronic hepatitis is a dynamic procedure indicating the interaction between HBV life cycle and the host genetic/ immune response, and not all patients with HBV infection have severe disease. Erefore, these genomic and biological variations within a tumor lesion are referred to as intratumor heterogeneity. Intratumoral heterogeneity of HCC, which can directly interact with tumor cells and affect the therapeutic response, has been considered as a critical aspect of cancer [4]

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