Abstract:

Objective　To investigate the correlation between Napsin A expression and the efficacy of second or later-line bevacizumab combined with chemotherapy in the treatment of advanced lung adenocarcinoma. Methods　The clinical data of 103 patients with stage IIIB-IV lung adenocarcinoma admitted to the 901st Hospital of the Joint Logistics Support Force of PLA from January 2018 to March 2022 were retrospectively analyzed. The expression of Napsin A protein was detected by the immunohistochemical EnVision method, and the mutations of epidermal growth factor receptor (EGFR), KRAS, and TP53 were detected by the amplification arrest mutation system (ARMS). The influencing factors of short-term efficacy, progression-free survival (PFS), and overall survival (OS) in patients with advanced lung adenocarcinoma treated with second or later-line bevacizumab combined with chemotherapy were analyzed. Follow-up was completed on December 31, 2023. χ² test was used for comparison between groups. Kaplan-Meier method was used to plot the survival curve and Log-rank test was used for comparison between groups. Cox proportional hazards regression model was used for multivariate analysis. Results　Among the 103 patients with advanced lung adenocarcinoma, there were 58 males and 45 females, with a median age of 63 years old, 30 cases had a history of smoking, 31 cases had brain metastases, and there were 67 cases of second-line treatment and 36 cases of third or later-line treatment. The chemotherapy regimens included pemetrexed and platinum in 73 cases, pemetrexed alone in 16 cases, docetaxel in 7 cases, and paclitaxel in 7 cases. The number of treatment cycles was ≥4 in 67 cases and <4 in 36 cases. There were 12 cases of KRAS mutation (11.7%), 18 cases of TP53 mutation (17.5%), and 50 cases of EGFR mutation (48.5%). There were 76 cases (73.8%) of Napsin A positive. The objective response rate (ORR) was 32.0% (33/103), and the disease control rate (DCR) was 79.6% (82/103); the DCR of Napsin A-negative patients was lower than that of Napsin A-positive patients (P<0.001). The median PFS was 6.4 months (95%CI: 5.9-6.9), and univariate analysis showed that the patients' PFS was related to the number of treatment lines (P=0.009), treatment cycle (P<0.001), Napsin A expression (P<0.001), KRAS mutation (P=0.012), and TP53 mutation (P=0.045). The median OS was 12.7 months (95%CI: 10.5-14.9), and univariate analysis showed that the patients' OS was related to treatment cycle (P=0.020), KRAS mutation (P=0.046), and Napsin A expression (P=0.001). Multivariate Cox regression analysis showed that Napsin A positivity (P=0.020), number of treatment cycles ≥4 (P=0.004), second-line treatment (P=0.009), and wild-type KRAS (P=0.012) were independent protective factors for PFS; Napsin A positivity (P=0.013) and wild-type KRAS (P=0.042) were independent protective factors for OS. Conclusion　Patients with advanced lung adenocarcinoma receiving second or later-line bevacizumab combined with chemotherapy have definite efficacy, and Napsin A positive and wild-type KRAS patients have better prognosis.

Key words:

Lung adenocarcinoma, Napsin A, Bevacizumab, Chemotherapy, Prognosis

摘要：

目的　探讨Napsin A蛋白表达与二线及以上贝伐珠单抗联合化疗方案治疗晚期肺腺癌疗效的相关性。方法　回顾性分析联勤保障部队第九○一医院2018年1月至2022年3月收治的103例ⅢB～Ⅳ期肺腺癌患者的临床资料。用免疫组化EnVision法检测Napsin A蛋白表达，用扩增阻滞突变系统（ARMS）检测驱动基因表皮生长因子受体（EGFR）、KRAS、TP53突变。分析二线及以上贝伐珠单抗联合化疗治疗晚期肺腺癌患者近期疗效、无进展生存期（PFS）、总生存期（OS）的影响因素。随访截止日期为2023年12月31日。组间比较采用χ²检验，采用Kaplan-Meier法绘制生存曲线并行Log-rank检验，采用Cox比例风险回归模型进行多因素分析。结果　103例晚期肺腺癌患者中男58例，女45例，中位年龄63岁，有吸烟史30例，脑转移31例，接受二线治疗67例、三线及以上治疗36例。化疗方案：培美曲塞联合铂类73例，培美曲塞单药16例，多西他赛7例，紫杉醇7例。治疗周期数≥4 67例，<4 36例。KRAS突变12例（11.7%），TP53突变18例（17.5%），EGFR突变50例（48.5%）。Napsin A阳性76例（73.8%）。103例患者客观缓解率（ORR）为32.0%（33/103），疾病控制率（DCR）为79.6%（82/103）；Napsin A阴性患者的DCR低于Napsin A阳性患者（P<0.001）。103例患者中位PFS为6.4个月（95%CI：5.9～6.9），单因素分析表明PFS与治疗线数（P=0.009）、治疗周期数（P<0.001）、Napsin A表达（P<0.001）、KRAS突变（P=0.012）、TP53突变（P=0.045）相关；中位OS为12.7个月（95%CI：10.5～14.9），单因素分析表明OS与治疗周期数（P=0.020）、KRAS突变（P=0.046）、Napsin A表达（P=0.001）相关。多因素Cox回归分析结果显示，Napsin A阳性（P=0.020）、治疗周期数≥4（P=0.004）、二线治疗（P=0.009）、野生型KRAS（P=0.012）是PFS的独立保护因素，Napsin A阳性（P=0.013）和野生型KRAS（P=0.042）是OS的独立保护因素。结论　晚期肺腺癌患者接受二线及以上贝伐珠单抗联合化疗效果确切，野生型KRAS和Napsin A阳性患者预后较好。

关键词:

肺腺癌, Napsin A, 贝伐珠单抗, 化疗, 预后