Keap1在非小细胞肺癌中的表达及与化疗疗效相关性的研究

Keap1 Expression for Predicting the Chemoresistance and Prognosis of Advanced Non-small Cell Lung Cancer

背景与目的已有研究表明Kelch样环氧氯丙烷相关蛋白1(Kelch-like ECH-associated protein1,Keap1)与铂类耐药相关。本研究旨在探讨Keap1在进展期非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及其与一线含铂化疗方案疗效的相关性。方法应用免疫组化检测50例进展期NSCLC患者组织标本中Keap1的表达。结果进展期NSCLC患者中Keap1高表达率为26.0%;Keap1表达水平与化疗疗效、无进展生存期(progression free survival,PFS)有关(P<0.05),而与性别、年龄、吸烟、病理类型、分化程度、转移和总生存期无关(P>0.05)。Keap1高表达组的中位PFS明显高于低表达组(P=0.002)。多因素分析表明Keap1表达水平是一线化疗方案PFS的独立预测因素(P=0.007)。结论 Keap1与进展期NSCLC一线化疗疗效和PFS有关,Keap1可能成为新的化疗疗效预测指标。

Background and objective It has been proven that Kelch-like ECH-associated protein 1 （Keapl） expression was correlated with the chemoresistance of platinum drugs. The aim of this study is to investigate the protein expres- sion levels of Keapl in non-small cell lung cancer （NSCLC） patients as well as to correlate its expression with the response rate （RR）, progression-free survival （PFS）, and overall survival （OS） of patients treated with platinum-based first-line chemother- apy. Methods The immunohistochemical analysis of Keapl expression was performed using tumor samples from 50 patients with stage III or IV NSCLC. Results The high expression ratio of Keapl was 26.0%. The Keap1 expression was significantly correlated with the RR and PFS after platinum-based chemotherapy （P〈0.05） but not with the gender, age, smoking1 pathol- ogy type, differentiation, metastasis, and OS （P〉0.05）. The PFS was significantly longer in patients with high Keapl expression than in those with low/negative expression （P=0.002）. Furthermorej the level of Keapl expression was an independent predic- tive factor of PFS after platinum-based first-line chemotherapy （P=0.007）. Conclusion The expression of Keap 1 was signifi- cantly correlated with the RR and PFS of platinum-based first-line chemotherapy. Therefore, Keap 1 may be a useful biomarker for predicting the chemosensitivity of patients with advanced-stage NSCLC.