RAD51 Expression as a Biomarker to Predict Efficacy of Preoperative Therapy and Survival for Esophageal Squamous Cell Carcinoma

Abstract

Objective:The aim of this study is to identify biomarkers that predict efficacy of preoperative therapy and survival for esophageal squamous cell carcinoma (ESCC).Background:It is essential to improve the accuracy of preoperative molecular diagnostics to identify specific patients who will benefit from the treatment; thus, this issue should be resolved with a large-cohort, retrospective observational study.Methods:A total of 656 patients with ESCC who received surgery after preoperative CDDP + 5-FU therapy, docetaxel + CDDP + 5-FU therapy or chemoradiotherapy (CRT) were enrolled. Immunohistochemical analysis of TP53, CDKN1A, RAD51, MutT-homolog 1, and programmed death-ligand 1 was performed with biopsy samples obtained before preoperative therapy, and expression was measured by immunohistochemistry.Results:In all therapy groups, overall survival was statistically separated by pathological effect (grade 3 > grade 2 > grade 0, 1, P < 0.0001). There was no correlation between TP53, CDKN1A, MutT-homolog 1, programmed death-ligand 1 expression, and pathological effect, whereas the proportion of positive RAD51 expression (≥50%) in cases with grade 3 was lower than that with grade 0, 1, and 2 (P = 0.022). In the CRT group, the survival of patients with RAD51-positive tumor was significantly worse than RAD51-negative expressors (P = 0.0119). Subgroup analysis of overall survival with respect to positive RAD51 expression indicated preoperative chemotherapy (CDDP + 5-FU or docetaxel + CDDP + 5-FU) was superior to CRT.Conclusions:In ESCC, positive RAD51 expression was identified as a useful biomarker to predict resistance to preoperative therapy and poor prognosis in patients who received preoperative CRT. Administration of preoperative chemotherapy may be warranted for patients with positive RAD51 expression.

New RAD51 Inhibitors to Target Homologous Recombination in Human Cells

“…High RAD51 expression leads to the resistance of tumors to chemotherapy with DNA-damaging agents, such as etoposide or cisplatin [ 62 , 65 ]. Elevated levels of RAD51 expression also correlate with a grade of a tumor [ 22 ] and poor disease prognosis [ 67 ]. In contrast, RAD51 knockdown was shown to increase the sensitivity of cancer cells to DNA-damaging agents [ 25 , 68 ].…”

Pan-immune-inflammation Value and Prognosis in Patients With Esophageal Cancer

“…[13][14][15] The identification of new biomarkers for good prognostic stratification and prediction of therapeutic outcomes for esophageal cancer is desperately needed in the clinical setting. [16][17][18] In particular, simple blood-based biomarkers derived from complete blood count, are readily available and inexpensive markers that can reflect the host immune system. 19 The pan-immune-inflammation value (PIV) is a recently proposed scoring system that includes all immune-inflammatory cells in the peripheral blood count (neutrophil count × platelet count × monocyte count)/lymphocyte count).…”

Regulation of RAD51 at the Transcriptional and Functional Levels: What Prospects for Cancer Therapy?

“…Thus, RAD51 is a crucial DNA repair actor in a large majority of cancers, notwithstanding their BRCA proficiency or deficiency. Consequently, it has been shown to be an interesting biomarker, as RAD51 expression levels have been proposed to be potentially predictive of resistance to treatment [143,144]. Additionally, assays aimed at determining the capacity of tumor cells to form RAD51 foci when challenged with a DNA-damaging treatment have been proposed as biomarkers of response to PARP-i (NCT04780945) [145].…”