High RAD51 Gene Expression is Associated with Aggressive Biology and with Poor Survival in Breast Cancer

Abstract

Purpose: Although DNA repair mechanism is a key to prevent carcinogenesis, its activation in established cancer cells may support their proliferation and aggravate cancer progression. RAD51 cooperates with BRCA2 and is essential in the homologous recombination of DNA repair. To this end, we hypothesized that RAD51 gene expression is associated with cancer cell proliferation and poor prognosis of breast cancer (BC) patients.Methods: A total of 8515 primary BC patients with transcriptome and clinical data from 17 independent cohorts were analyzed. Median was used to divide each cohort into high and low RAD51 expression groups.Results: High RAD51 expression enriched DNA repair gene set and was correlated with DNA repair-related genes. Nottingham histological grade, Ki67 expression and cell proliferation-related gene sets (E2F Targets, G2M Checkpoint and Myc Targets) were all significantly associated with the high RAD51 BC. RAD51 expression was positively correlated with Homologous Recombination Deficiency, as well as both mutation burden and neoantigen that accompanied with higher infiltration of immune cells. Primary BC with lymph node metastases were associated with high expression of RAD51 in 2 cohorts. There was no strong correlation between RAD51 expression and drug sensitivity in cell lines, and RAD51 expression was lower after the neoadjuvant chemotherapy compared to before the treatment. High RAD51 BC was associated with poor prognosis consistently in 3 independent cohorts.Conclusion: RAD51 gene expression is associated with aggressive cancer biology, cancer cell proliferation, and poor survival in breast cancer.

Taurohyocholic acid acts as a potential predictor of the efficacy of tyrosine kinase inhibitors combined with programmed cell death-1 inhibitors in hepatocellular carcinoma

“…Furthermore, a similar phenomenon has been observed in patients with breast cancer, with a robust connection between plasma BA metabolite composition, host immune activation, and therapeutic response (Wu et al, 2022).…”

KIF5A upregulation in hepatocellular carcinoma: A novel prognostic biomarker associated with unique tumor microenvironment status

“…According to the analyses of immune scores, a high level of lymphocyte signature score, TCR richness and BCR richness were significantly correlated with high KIF5A expression in LIHC (Figure 7C). Thus, activation of multiple antitumor immune responses was associated with KIF5A expression in LIHC (28,41). Given that tumor mutations can generate neoantigens which could subsequently prime a T-cell immune attack to tumor cells, we explored immune scores that related to neoantigens, including homologous recombination defects, intratumor heterogeneity, number of segments and faction altered (28,42).…”