Identification of Key Genes in the HBV-Related HCC Immune Microenvironment Using Integrated Bioinformatics Analysis

Wei Ding; Zheng Zhang; Nianyuan Ye; Ling Zhuang; Zhiping Yuan; Wenbo Xue; Yulin Tan; Xuezhong Xu

doi:10.1155/2022/2797033

Identification of Key Genes in the HBV-Related HCC Immune Microenvironment Using Integrated Bioinformatics Analysis

J Oncol. 2022 Oct 15:2022:2797033. doi: 10.1155/2022/2797033. eCollection 2022.

Authors

Wei Ding^#^{1

2

3}, Zheng Zhang^#^{1

2}, Nianyuan Ye^#^{1

2}, Ling Zhuang^{1

2}, Zhiping Yuan^#⁴, Wenbo Xue^{1

2}, Yulin Tan^{1

2}, Xuezhong Xu^{1

2}

Affiliations

¹ Department of General Surgery, Wujin Hospital Affiliated to Jiangsu University, Changzhou 213017, China.
² Department of General Surgery, The Wujin Clinical College of Xuzhou Medical University, Changzhou 213017, China.
³ Changzhou Key Laboratory of Molecular Diagnostics and Precision Cancer Medicine, Changzhou 213017, China.
⁴ Department of Gastroenterology, Wujin Hospital Affiliated with Jiangsu University, Changzhou 213017, China.

^# Contributed equally.

Abstract

Purpose: Hepatocellular carcinoma (HCC) has poor prognosis and high mortality among gastrointestinal tumors because of its insidious onset and strong invasiveness. However, there was little understanding of their pathogenesis. The purpose of this study was to use bioinformatics analysis to identify genes associated with the immune microenvironment in HBV-related HCC and to develop new therapeutic targets to prevent and treat cancer.

Methods: RNA-seq data of HBV-related HCC cases were downloaded from TCGA-LIHC database. ESTIMATE and Deseq2 algorithms were used to screen out differentially expressed genes (DEGs). WGCNA was used to construct gene coexpression networks. In key modules, functional enrichment analysis was performed. Protein-protein interaction (PPI) was used to screen hub genes, and survival analysis was conducted to assess their prognostic significance. Following, we search for key genes differentially expressed between cancerous and paracancerous tissues in GSE136247 and GSE121248 datasets. Reveal the potential links between key genes in immune infiltration by using TIMER. Finally, in TCGA-LIHC database, integration of key genes with clinical data were used to further validate their correlation with prognosis.

Results: In the cohort of HBV-related HCC patients, immune/stromal/ESTIMATE scores were not significantly associated with patient prognosis. After bioinformatics analysis, screening out five key genes was significantly related to the prognosis of HBV-related HCC. Downregulation of SLAMF1 and TRAF3IP3 suggested poor prognosis and was related to a variety of immune cell infiltration. Furthermore, compared with adjacent nontumor tissues, TRAF3IP3 and SLAMF1 were highly expressed in tumor tissues and were linked to tumor recurrences.

Conclusion: In conclusion, SLAMF1 and TRAF3IP3 were identified with higher expression in tumor tissues and associated with tumor recurrence. It will be a new research direction of tumor progress and treatment.