【摘要】 目的 探讨肺腺癌所致恶性胸腔积液中G蛋白偶联雌激素受体(GPER)的表达状态及其对患者接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗结果的影响。方法 回顾分析2017年1月1日至2021年12月31日期间在汕头大学医学院第二附属医院初次诊断时出现恶性胸腔积液的肺腺癌患者的临床资料,免疫组化检测患者恶性胸腔积液来源细胞块中GPER的表达情况,比较GPER不同表达患者的EGFR-TKI治疗反应,采用Kaplan-Meier法和log-rank检验比较患者无进展生存期(PFS)的差异;构建Cox风险比例回归模型分析影响患者PFS的独立危险因素。结果 106例患者中GPER阳性68例、阴性38例;GPER阴性患者的客观缓解率高于GPER阳性患者[73.7%(28/38) vs. 48.5%(33/68),χ~2=6.314,P=0.012],而GPER阴性患者的疾病控制率与GPER阳性患者的差异无统计学意义[97.4%(37/38) vs. 88.2%(59/68),P=0.092]。单因素分析显示GPER阴性患者的中位PFS为13.2个月,优于GPER阳性患者的10.6个月(P=0.035);多因素分析结果显示,GPER阳性是影响伴有恶性胸腔积液的肺腺癌患者PFS的独立危险因素(HR=2.041,95%CI:1.303～3.196,P=0.002)。结论 伴恶性胸腔积液的晚期肺腺癌GPER的高表达是这类患者EGFR-TKI疗效的负性预测指标,可能是潜在的预测生物标志物及治疗靶点。更多还原

【Abstract】 Objective To investigate the effect of G protein-coupled estrogen receptor( GPER) expression status in malignant pleural effusion due to lung adenocarcinoma on the outcome of patients treated with epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI). Methods Clinical data of lung adenocarcinoma patients who presented with malignant pleural effusion at the initial diagnosis in the Second Affiliated Hospital of Shantou University Medical College between January 1, 2017 and December 31, 2021 were retrospectively analyzed. Expression of GPER in the cell block of malignant pleural effusion origin of the patients was detected by immunohistochemistry, and the response to EGFR-TKI treatment was compared between patients with different GPER expression. Kaplan-Meier method and log-rank test were used to compare the difference in progression-free survival(PFS) of patients.The Cox proportional hazards model was constructed to analyze the independent risk factors affecting the PFS of the patients. Results Among 106 patients, 68 were GPER positive and 38 were GPER negative. The objective response rate of GPER negative patients was higher than that of GPER positive patients [73. 7%(28/38) vs. 48. 5%(33/68), χ~2= 6. 314, P= 0. 012], while the difference in disease control rate between GPER negative patients and GPER positive patients was not statistically significant [97. 4%(37/38) vs.88. 2%(59/68), P= 0. 092]. Univariate analysis showed that the median PFS of GPER negative patients was 13. 2 months, better than that of GPER positive patients at 10. 6 months(P= 0. 035). Results of multivariate analysis showed that GPER positivity was an independent risk factor for PFS in lung adenocarcinoma patients with malignant pleural effusion( HR = 2. 041, 95% CI: 1. 303-3. 196, P= 0. 002). Conclusion High expression of GPER in advanced lung adenocarcinoma with malignant pleural effusion is a negative predictor of EGFR-TKI efficacy in these patients and may be a potential predictive biomarker and therapeutic target.更多还原