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Low BRCA2 expression predicts poor prognoses in patients with rectal cancer receiving chemoradiotherapy
Ming-Jen Sheu1, Chia-Lin Chou2, Ching-Chieh Yang3
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; Department of Medicinal Chemistry, Chia Nan University, Tainan, Taiwan.
Objective:
Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is now the standard care for patients with advanced rectal cancer. Because a certain proportion of these patients have poor response to CCRT, the risk stratification of survival outcomes needs to be investigated. DNA repair responses in tumor cells can regulate malignant potential and therapy resistance. In this study, we analyzed the clinical significance of principal DNA repair effectors in patients with rectal cancer.
Methods:
We applied data mining for DNA repair pathways in a published transcriptome for rectal cancer cases, and identified that tumors with BRCA2 downregulation correlated with poor response to CCRT. We next examined BRCA2 expression by using immunohistochemistry staining in tumor tissues of 172 patients with rectal cancer. The correlation between BRCA2 expression levels and clinical variables was further analyzed in this rectal cancer cohort.
Results:
Among clinical and pathological factors, low BRCA2-expression was significantly correlated with higher pre-treatment (Tx) tumor status (P = .013), post-Tx tumor (P < .001) and nodal status (P = .044), vascular invasion (P = .008), and poor tumor regression grades (P < .001). In analyses of survival outcomes, patients with low BRCA2-expression were associated with shorter local recurrence-free survival (LRFS; P = .0005) and disease-specific survival (P = .0269). Multivariate analyses confirmed the independent prognostic value of low BRCA2-expression for shorter LRFS (P = .045, hazard ratio = 4.695).
Conclusion:
Low BRCA2-expression is a significant predictor for tumors in advanced stages, poor response to CCRT, and shorter survivals in patients with rectal cancer. Poly (adenosine diphosphate-ribose) polymerase inhibitors targeting DNA repair response in cells have demonstrated clinical efficacy in BRCA2-mutated patients with cancer. Further studies evaluating the efficacy of CCRT combined with these inhibitors in low BRCA2-expressing rectal cancers are encouraged.
