表皮生长因子受体和转移抑制基因23表达对直肠癌术后患者预后的影响

Prognostic value of epidermal growth factor receptor and nm23 expression in patients with rectal cancer and its guiding significance for treatment

目的探讨表皮生长因子受体（EGFR）和转移抑制基因23（nm23）蛋白表达与直肠癌术后患者预后的关系，寻找可靠的预后预测因子组合。方法 采用免疫组织化学染色法检测243例直肠癌组织中EGFR和nm23蛋白的表达，记录患者病理及临床资料，并进行随访。运用Kaplan-Meier、Cox回归及分层分析评估直肠癌组织中EGFR和nm23蛋白的表达与直肠癌术后患者无进展生存期（PFS）之间的关系。结果免疫组织化学结果显示EGFR和nm23在直肠癌组织中均有表达。Kaplan-Meier分析结果显示，EGFR高表达的直肠癌术后患者预后较差，中位PFS为21.0个月，低表达患者的预后较好，中位生存期为37.8个月（χ2＝8.687，P＝0.003）；而nm23高表达的直肠癌术后患者预后较好，中位PFS为35.4个月，低表达患者预后较差，中位PFS为13.4个月（χ2＝15.593，P＝0.001）。EGFR低表达且nm23高表达的患者PFS更长，中位PFS为62.9个月（χ2＝18.227，P＝0.000）。单因素分析结果显示，相较于EGFR低表达且nm23高表达的直肠癌术后患者，EGFR高表达且nm23低表达患者肿瘤进展的风险更高[风险比（HR）＝2.290，95%可信区间（CI）：1.548～3.387，P＝0.000]。多因素分析（Cox）发现，EGFR和nm23可作为直肠癌术后患者预后的联合预测因子（HR＝1.966，95%CI：1.319～2.929，P＝0.001）。此外，分层分析结果也表明，Dixon手术后EGFR低表达且nm23高表达的患者较其他患者预后更好，中位PFS为62.9个月（χ2＝9.170，P＝0.003），且在此类患者中，接受FOLFOX4方案化疗的患者较其他患者PFS更长，中位PFS为61.1个月（χ2＝8.218，P＝0.004）。结论EGFR和nm23可用于直肠癌术后患者预后的判断，并且是一对较理想的预后预测因子组合。

Objective To evaluate the predictive value of epidermal growth factor receptor （EGFR） and nm23 expression and its guiding role of choosing chemotherapy regimen in post-operation patients with rectal carcinoma.Methods The expression of EGFR and nm23 in 243 specimens of rectal carcinoma tissues was examined by immunohistochemistry. The clinical and pathological data were recorded, and patients were followed up for more than five years. Kaplan-Meier estimates, Cox proportional hazard regression and hierarchical analyses were employed to assess the correlation between the expression of EGFR and nm23 in rectal carcinoma and the progression free survival （PFS） of patients treated with the different surgical methods and chemotherapy.Results EGFR and nm23 were expressed proportionately in rectal cancer tissues. Kaplan-Meier showed that EGFR expression is negatively related to the PFS of the post-operative patients. The median PFS was 21.0 months in the patients with high expression, and that was 37.8 months in the patients with low expression （χ2=8.687, P=0.003）. The nm23 expression was positively associated with the PFS of the post-operative patients. The median PFS was 35.4 months in the patients with high expression, and that was 13.4 months in the patients with low expression （χ2=15.593, P=0.001）. The median PFS was longer in the patients with low EGFR expression and high nm23 expression （median PFS=62.9 months, χ2=18.227, P=0.000）. The univariate analyses revealed that the patients with low EGFR expression and high nm23 expression had longer PFS than in those with high EGFR expression and low nm23 expression[hazard ratio （HR）=2.290, 95% confidence interval （CI）： 1.548-3.387, P=0.000]. Multivariate analysis （Cox） showed that low EGFR expression and high nm23 expression was an independent combined predictor of longer PFS （HR=1.966, 95%CI： 1.319-2.929, P=0.001）. In addition, hierarchical analysis also suggested that post-Dixon operation patients with low EGFR expression and high nm23 expression had significantly longer survival time than other patients, and also were more sensitive to chemotherapy with FOLFOX4 regimen than other patients （median PFS=61.1 months, χ2=8.218, P=0.004）.Conclusion EGFR and nm23 have predictive value for the prognosis of post-operative patients with rectal carcinoma and are an ideal combination of predictive factors.