Correlations of β-catenin expression with clinical efficacy of tyrosine kinase inhibitors and prognosis of advanced lung adenocarcinoma patients with epidermal growth factor receptor mutations / 肿瘤研究与临床

ABSTRACT

Objective:To investigate the correlations of β-catenin expression with the efficacy of tyrosine kinase inhibitor (TKI) and prognosis of patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.Methods:The clinical data of 125 patients with stage Ⅲ B-Ⅳ lung adenocarcinoma who were treated with first-line EGFR-TKI treatment in the 901st Hospital of Joint Logistic Support Force of Chinese PLA from January 2016 to December 2019 were collected. The expression of β-catenin protein was detected by immunohistochemistry, and subtypes of EGFR mutations were detected by amplification refractory mutation system (ARMS). Correlations of β-catenin expression with clinicopathological features, efficacy of EGFR-TKI and prognosis were analyzed. Twenty-eight pairs of specimens were selected before EGFR-TKI treatment and after resistance to EGFR-TKI to observe the changes of β-catenin expression. Results:Among 125 advanced lung adenocarcinoma patients with EGFR mutations, there were 60 cases of EGFR 19 del, 55 cases of L858R mutation and 10 cases of rare sensitive mutation; 79 cases (63.2%) had reduced membranous expression of β-catenin, 66 cases (52.8%) had ectopic expression in cytoplasm and 28 cases (22.4%) had ectopic expression in nucleus. The positive rates of Napsin A protein in the groups with different abnormal expression patterns of β-catenin were lower than those in the corresponding normal expression groups (all P < 0.001). Patients with International Association for the Study of Lung Cancer (IASLC) grade Ⅲ showed more frequent translocation in cytoplasma and nucleus of β-catenin than patients with IASLC gradeⅠ-Ⅱ (ectopic expression in cytoplasm χ2 = 3.99, P = 0.046,ectopic expression in nucleus χ2 = 11.07, P = 0.001). The objective remission rate (ORR) in patients with reduced membranous expression of β-catenin and ectopic expression in nucleus was lower than that in patients with normal membranous expression ( χ2 = 4.66, P = 0.031) and negative ectopic expression in nucleus ( χ2 = 10.22, P = 0.001), and the disease control rate (DCR) in patients with ectopic expression in nucleus was lower than that in the corresponding normal expression group ( χ2 = 10.95, P = 0.001). Patients with ectopic expression of β-catenin in nucleus and cytoplasma had worse progression-free survival (PFS) and overall survival (OS) than the corresponding cytoplasmic and nuclear ectopic expression negative groups (both P < 0.05). Multivariate Cox regression analysis showed that nuclear β-catenin ectopic expression was an independent risk factor for both PFS and OS (PFS HR = 2.088, 95% CI 1.331-3.274, P = 0.001; OS HR = 3.656, 95% CI 1.795-7.444, P<0.001). β-catenin membranous expression was reduced in 11 of 28 tissue samples that underwent secondary biopsy compared with pre-treatment ( P = 0.049). Conclusions:β-catenin expression in advanced lung adenocarcinoma with EGFR-sensitive mutations can be used as a molecular marker to predict the efficacy of EGFR-TKI and prognosis of patients.