Prognostic and Predictive Role of JWA and XRCC1 Expressions in Gastric Cancer

Abstract

Purpose: To investigate the expression pattern and significance of DNA repair genes JWA and X-ray repair cross complement group 1 (XRCC1) in gastric cancer.Experimental Design: Expressions of JWA and XRCC1 were assessed by immunohistochemistry in a training cohort and they went into a second testing cohort and finally to a validating cohort. Prognostic and predictive role of JWA and XRCC1 expression status in cases treated with surgery alone or combined with adjuvant chemotherapy was evaluated, respectively.Results: JWA and XRCC1 protein levels were significantly downregulated in gastric cancer lesions compared with adjacent noncancerous tissues. Low tumoral JWA or XRCC1 expression significantly correlated with shorter overall survival (OS), as well as with clinicopathologic characteristics in patients without adjuvant treatment. Multivariate regression analysis showed that low JWA and XRCC1 expressions, separately and together, were independent negative markers of OS. Adjuvant fluorouracil-leucovorinoxaliplatin (FLO) significantly improved OS compared with surgery alone (log-rank test, P ¼ 0.01). However, this effect was evident only in the JWA or XRCC1 low expression group (HR ¼ 0.44; 95% CI: 0.26-0.73; P ¼ 0.002, and HR ¼ 0.44, 95% CI: 0.26-0.75; P ¼ 0.002, respectively); Adjuvant fluorouracilleucovorin-platinol (FLP) did not improve OS, except in the patients with low JWA and XRCC1 expressions (P ¼ 0.010 for JWA and 0.024 for XRCC1, respectively).Conclusions: JWA and XRCC1 protein expressions in tumor are novel candidate prognostic markers and predictive factors for benefit from adjuvant platinum-based chemotherapy (FLO or FLP) in resectable human gastric carcinoma.

JWA deficiency induces malignant transformation of murine embryonic fibroblast cells

“…JWA has been previously reported as a novel regulator in inhibiting melanoma cell adhesion, invasion and metastasis (7) and has been demonstrated to have prognostic and predictive roles in gastric cancer (13). In the present study, JWA -/-was able to increase MEF cell proliferation, and stimulate cell migration, cell invasion and colony formation, ultimately promoting malignant transformation in MEF cells.…”

DNA Base Excision Repair: Evolving Biomarkers for Personalized Therapies in Cancer

“…However, this effect was evident only in the XRCC1 low expression group (HR 0.44, 95% CI 0.26-0.75; P 0.002); Adjuvant fluorouracil-leucovorin-platinum (FLP) did not improve OS, except in the patients with low XRCC1 expressions (P 0.024). XRCC1 protein expressions in tumour are novel candidate prognostic markers and predictive factors for benefit from adjuvant platinum-based chemotherapy (FLO or FLP) in patients with resectable gastric carcinoma [75]. SMUG1, FEN1, XRCC1 and ATM are involved in ROS induced oxidative DNA damage repair in gastric cancer patients.…”

3,3′-diindolylmethane potentiates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of gastric cancer cells

“…Western blot analysis was conducted as previously described (11). Briefly, cells were lysed by incubating in lysis buffer (50 mM Tris, 150 mM NaCl, 1% Triton X-100, 1% sodium deoxycholate, 0.1% SDS; pH 7.4; Beyotime Institute of Biotechnology) for 20 min at 4˚C and the protein concentration was determined using the Beyotime assay system (Beyotime Institute of Biotechnology).…”