Prognostic and predictive role of JWA and XRCC1 expression in gastric cancer
Menée sur trois cohortes consécutives de patients atteints d'un cancer de l'estomac, cette étude évalue l'intérêt de mesurer l'expression tumorale de deux gènes impliqués dans la réparation de l'ADN, JWA et XRCC1, pour prédire la réponse à une chimiothérapie adjuvante à base de sels de platine
Purpose: To investigate the expression pattern and significance of DNA repair genes JWA and 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 non-cancerous 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 expression, separately and together, were independent negative markers of OS. Adjuvant fluorouracil-leucovorin-oxaliplatin (FLO) significantly improved OS compared with surgery alone (log-rank test, P = 0.01). However, this effect was evident only in the JWA or XRCC1 low expression group (HR = 0.44; 95% CI = 0.26-0.73; P = 0.002, and HR = 0.44; 95% CI = 0.26-0.75; P = 0.002, respectively); Adjuvant fluorouracil-leucovorin-platinol (FLP) did not improve OS, except in the patients with low JWA and XRCC1expression (P = 0.010 for JWA and P = 0.024 for XRCC1, respectively). Conclusions: JWA and XRCC1 protein expression 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.
Clinical Cancer Research , résumé, 2012