Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets, Buffalo, NY, 14263, USA.
Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, 160-8402, Japan.
Breast Cancer Res Treat. 2022 May;193(1):49-63. doi: 10.1007/s10549-022-06552-0. Epub 2022 Mar 6.
Although the DNA repair mechanism is important in preventing 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.
A total of 8515 primary BC patients with transcriptome and clinical data from 17 independent cohorts were analyzed. The median value was used to divide each cohort into high and low RAD51 expression groups.
High RAD51 expression enriched the 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 group. RAD51 expression was positively correlated with Homologous Recombination Deficiency, as well as both mutational burden and neoantigens that accompanied a higher infiltration of immune cells. Primary BC with lymph node metastases was associated with high expression of RAD51 in two 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 three independent cohorts.
RAD51 gene expression is associated with aggressive cancer biology, cancer cell proliferation, and poor survival in breast cancer.
尽管 DNA 修复机制对于预防致癌作用非常重要，但它在已建立的癌细胞中的激活可能会支持其增殖并加剧癌症的进展。RAD51 与 BRCA2 合作，是 DNA 修复同源重组所必需的。为此，我们假设 RAD51 基因表达与乳腺癌（BC）患者的癌细胞增殖和不良预后有关。
分析了来自 17 个独立队列的 8515 名原发性 BC 患者的转录组和临床数据。使用中位数将每个队列分为高和低 RAD51 表达组。
高 RAD51 表达丰富了 DNA 修复基因集，并与 DNA 修复相关基因相关。诺丁汉组织学分级、Ki67 表达和细胞增殖相关基因集（E2F 靶标、G2M 检查点和 Myc 靶标）均与高 RAD51 BC 组显著相关。RAD51 表达与同源重组缺陷以及突变负担和伴随免疫细胞浸润增加的新抗原呈正相关。两个队列的淋巴结转移原发性 BC 与 RAD51 高表达相关。在细胞系中，RAD51 表达与药物敏感性之间没有很强的相关性，并且与治疗前相比，新辅助化疗后 RAD51 表达降低。在三个独立的队列中，高 RAD51 BC 与预后不良一致相关。
RAD51 基因表达与乳腺癌中侵袭性癌症生物学、癌细胞增殖和不良生存相关。
