Identification of Rad51 as a prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma

Bioengineered. 2021 Dec;12(1):2664-2675. doi: 10.1080/21655979.2021.1938470.

Abstract

Rad51, a DNA-repair-related gene, has been reported to be involved in multiple cancers. However, its link with immune infiltration in liver cancer still unknown. Therefore, more research into the roles and activities of Rad51 in hepatocellular carcinoma (HCC) is required. The International Cancer Genome Consortium (ICGC) was used to identify the DNA repair gene Rad51, and has been proved to be overexpressed in HCC patients. We plotted the Kapan-Meier curve, demonstrating that patients with high expression of Rad51 have a poor prognosis. By analyzing the patient data, we discovered that high expression of Rad51 in HCC is linked to clinical stage, pathological T stage, grade, and age. Rad51 was found to be an independent prognostic factor for HCC patients using the multivariate cox model. Moreover, Rad51 expression was found to be associated with the infiltration of immune cells (B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells) and was intimately linked to the expression of immune cell markers in HCC. Through the analysis of differentially coexpressed genes (DCGs) of Rad51, GO and KEGG enrichment analyses suggested that the expression level of Rad51 might be relevant to neuroactive ligand-receptor interactions, the cell cycle, DNA replication, homologous recombination, oocyte meiosis, and the Fanconi anemia pathway. These findings indicated that Rad51 is a valuable biomarker for the prognosis of patients with liver cancer and that its expression has a significant correlation with immune infiltrations.Abbreviations: HCC: hepatocellular carcinoma; ICGC: International Cancer Genome Consortium TCGA: The Cancer Genome Atlas; TIMER: Tumor Immune Estimation Resource; CAF: Cancer-associated fibroblast; GEPIA: Gene Expression Profiling Interactive Analysis; GSEA: Gene set enrichment analysis; OS: overall survival; PFS: progression-free survival; RFS: relapse-free survival; DSS: disease-specific survival. Partial cor: partial correlation coefficient; HPA: Human Protein Atlas; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; CAF: Cancer-associated fibroblast; DCGs: differentially co-expressed genes.

Keywords: DNA repair gene; Hepatocellular carcinoma; ICGC; TCGA; immune infiltration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / pathology
  • DNA Repair / genetics
  • Databases, Genetic
  • Female
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Male
  • Neoplasm Invasiveness* / genetics
  • Neoplasm Invasiveness* / pathology
  • Prognosis
  • Rad51 Recombinase / genetics*
  • Rad51 Recombinase / metabolism

Substances

  • Biomarkers, Tumor
  • RAD51 protein, human
  • Rad51 Recombinase

Grants and funding

This work was supported by The National Natural Science Foundation of China under Grant number 81871909; “13th five-year Plan“ Science and Education strong Health Project leading personnel of Yangzhou under Grant number YZCXTD201801; Provincial-level discipline leader of the NJPH under Grant number DTRC201809;The National Natural Science Foundation of China [81871909];Provincial-level discipline leader of the NJPH [DTRC201809];”13th five-year Plan” Science and Education strong Health Project leading personnel of Yangzhou [YZCXTD201801];