Expression and Prognostic Value of RAD51 in Adenocarcinoma at the Gastroesophageal Junction

Abstract

Background: The RAD51 recombinase is involved in homologous recombination and DNA repair. However, the association of RAD51 with the prognosis of adenocarcinoma at the gastroesophageal junction (ACGEJ) is not clear. We aimed to investigate the association of RAD51with ACGEJ prognosis.
 Methods: The difference in the expression level of RAD51 between ACGEJ tumors and control tissues in the microarray datasets (GSE159721, GSE74553, and GSE96669) were compared. The online Kaplan-Meier plotter survival analysis and meta-analysis were used to analyze the association of RAD51 with overall survival in pan-cancers. MiRNAs targeting RAD51 were identified and their expression profiles in ACGEJ tumors were analyzed. Functional enrichment analysis was performed for miRNAs of RAD51.
 Results: RAD51 was upregulated in ACGEJ tumors compared with control tissues (P < 0.05). High RAD51 level was correlated with a poor prognosis in stomach adenocarcinoma and esophageal cancer. The meta-analysis showed that high RAD51 level was correlated with a poor prognosis in TCGA pan-cancers (P = 0.03). Six regulatory miRNAs of RAD51, including hsa-miR-182, hsa-miR-221, and hsa-miR-34a, were downregulated in ACGEJ tumor tissues and were associated with pathways including “fatty acid biosynthesis” and “viral carcinogenesis”.
 Conclusions: RAD51 is a potent prognostic biomarker in ACGEJ. MiRNAs including hsa-miR-182, hsa-miR-221, and hsa-miR-34a might play crucial roles in ACGEJ by regulating the RAD51 gene.

mRNA Expression and Methylation of the RAD51, ATM, ATR, BRCA1, and BRCA2 Genes in Gastric Adenocarcinoma

“…In contrast to our finding, Redati et al 37 noted that high levels of RAD51 mRNA are associated with greater survival in gastric adenocarcinoma and esophageal squamous cell carcinoma, but with a worse prognosis in hepatocellular carcinoma and esophageal, breast, lung, and gastroesophageal junction adenocarcinomas.…”

“…In addition, the microRNAs miR-182, miR-221, miR-34a, and miR-766 inhibit the synthesis of the RAD51 protein. 37 Additionally, RAD51 is ubiquitinated and undergoes degradation by FBH1, FBXO5, and RFWD3. 38 …”