Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment, Cancer Center; School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
Clin Cancer Res. 2012 May 15;18(10):2987-96. doi: 10.1158/1078-0432.CCR-11-2863. Epub 2012 Mar 27.
To investigate the expression pattern and significance of DNA repair genes JWA and X-ray repair cross complement group 1 (XRCC1) in gastric cancer.
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.
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-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 XRCC1 expressions (P = 0.010 for JWA and 0.024 for XRCC1, respectively).
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.
研究 DNA 修复基因 JWA 和 X 射线修复交叉互补组 1（XRCC1）在胃癌中的表达模式和意义。
在训练队列中，通过免疫组织化学评估 JWA 和 XRCC1 的表达情况，然后将其纳入第二个测试队列，最终纳入验证队列。分别评估 JWA 和 XRCC1 表达状态对单独手术或联合辅助化疗治疗病例的预后和预测作用。
与相邻非癌组织相比，胃癌病变中 JWA 和 XRCC1 蛋白水平显著下调。低肿瘤 JWA 或 XRCC1 表达与无辅助治疗患者的总生存期（OS）以及临床病理特征显著相关。多变量回归分析显示，低 JWA 和 XRCC1 表达，分别和共同，是 OS 的独立负标记物。与单独手术相比，氟尿嘧啶-亚叶酸钙-奥沙利铂（FLO）辅助治疗显著改善了 OS（对数秩检验，P = 0.01）。然而，这种效果仅在 JWA 或 XRCC1 低表达组中明显（HR = 0.44；95%CI：0.26-0.73；P = 0.002，和 HR = 0.44；95%CI：0.26-0.75；P = 0.002）；氟尿嘧啶-亚叶酸钙-顺铂（FLP）辅助治疗不能改善 OS，除了 JWA 和 XRCC1 低表达的患者（JWA 为 P = 0.010，XRCC1 为 P = 0.024）。
肿瘤中 JWA 和 XRCC1 蛋白表达是新的候选预后标志物和预测因素，可预测可切除人胃癌从辅助铂类化疗（FLO 或 FLP）中获益。
