治疗前脂蛋白(a)作为肺腺癌表皮生长因子受体突变及预后的生物标志物

Pretreatment Lipoprotein(a) as a Biomarker for EGFR Mutation and Prognosis in Lung Adenocarcinoma.

作者信息

Liu Ji, Liu Zhekang, Xu Deming, Zhou Tao, Li Ang, Hu Jiali, Li Hong, Li Wenjie, Wang Zengqing, Yu Zhiping, Zeng Linxiang

机构信息

Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.

Rheumatology and Immunology department, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People's Republic of China.

出版信息

Int J Gen Med. 2024 Dec 27;17:6465-6478. doi: 10.2147/IJGM.S501401. eCollection 2024.

DOI:10.2147/IJGM.S501401

PMID:39742033

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11687294/

Abstract

PURPOSE

This study aims to investigate the correlation between pretreatment serum lipoprotein(a) [Lp(a)] and epidermal growth factor receptor (EGFR) gene mutations, as well as its predictive value for progression-free survival (PFS) in advanced lung adenocarcinoma patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy.

PATIENTS AND METHODS

We determined the optimal cutoff value for Lp(a) by receiver operating characteristic (ROC) curves and Youden's index to categorize Lp(a) into high and low groups. Logistic regression was used to analyze the EGFR mutation rate in different groups. Additionally, the relationship between pretreatment Lp(a) levels and prognostic PFS in patients with advanced (TNM stage IIIB-IV) lung adenocarcinoma treated with EGFR-TKIs was retrospectively analyzed by Cox regression, survival and stratified analysis methods.

RESULTS

We included 338 advanced lung adenocarcinoma patients, with median age of 64 years, and slightly more female patients (51.8%), most of whom had no smoking history (70.7%), no history of chronic lung disease (87.9%), and stage IV (81.1%) patients. The EGFR gene mutation rate was 55.3% and 123 patients were included in the prognostic evaluation through screening. The optimal cutoff value for Lp(a) was 20.48 mg/L. The mutation rate in the high Lp(a) group was significantly lower than the low Lp(a) group (48.0% vs 65.5%, = 0.001). Multivariate logistic regression analysis indicated that Lp(a) is an independent predictor of EGFR mutations (OR = 0.41, 95% CI: 0.25-0.66, <0.001). Survival analysis showed that the median PFS was significantly longer in the high Lp(a) level group compared to the low level group (16.1 months, 95% CI: 11.9-23.8 months vs 9.6 months, 95% CI: 8.9-13.3 months, =0.015). Multivariate analysis confirmed that Lp(a) is an independent predictor of PFS in advanced lung adenocarcinoma patients receiving EGFR-TKIs treatment (HR = 0.42, 95% CI: 0.26-0.68, <0.001).

CONCLUSION

Pretreatment Lp(a) may be a biomarker for EGFR mutations and the PFS in advanced lung adenocarcinoma patients undergoing EGFR-TKIs treatment.

摘要

目的

本研究旨在探讨治疗前血清脂蛋白(a)[Lp(a)]与表皮生长因子受体(EGFR)基因突变之间的相关性，及其对接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗的晚期肺腺癌患者无进展生存期(PFS)的预测价值。

患者与方法

我们通过受试者工作特征(ROC)曲线和尤登指数确定Lp(a)的最佳截断值，将Lp(a)分为高、低两组。采用逻辑回归分析不同组的EGFR突变率。此外，采用Cox回归、生存分析和分层分析方法，回顾性分析接受EGFR-TKIs治疗的晚期（TNM分期IIIB-IV期）肺腺癌患者治疗前Lp(a)水平与预后PFS之间的关系。

结果

我们纳入了338例晚期肺腺癌患者，中位年龄为64岁，女性患者略多(51.8%)，其中大多数无吸烟史(70.7%)，无慢性肺病病史(87.9%)，IV期患者占81.1%。EGFR基因突变率为55.3%，通过筛选有123例患者纳入预后评估。Lp(a)的最佳截断值为20.48mg/L。高Lp(a)组的突变率显著低于低Lp(a)组(48.0%对65.5%，P=0.001)。多因素逻辑回归分析表明，Lp(a)是EGFR突变的独立预测因子(OR=0.41，95%CI：0.25-0.66，P<0.001)。生存分析显示，高Lp(a)水平组的中位PFS显著长于低水平组(16.1个月，95%CI：11.9-23.8个月对9.6个月，95%CI：8.9-13.3个月，P=0.015)。多因素分析证实，Lp(a)是接受EGFR-TKIs治疗的晚期肺腺癌患者PFS的独立预测因子(HR=0.42，95%CI：0.26-0.68，P<0.001)。