Distinct Role of TP53 Co-mutations in Different EGFR Subtypes Mediating the Response to EGFR Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer

作者：Lihong Wei, Yi Lao, Tongze Fu, Zhongpeng Xie, Yanxia Wang, Tiantian Yang, Leilei Huang, Jiahua Liu, Man Shu, Tian Tian, Shuhua Li, Qiong He, Jianwen Zhou, Xu‐Chao Zhang, Huipin Wang, Juan Du, Xinwei Wang, Zheng Yang, Lihong Bai, Zunfu Ke · 发表于：Clinical Lung Cancer · 年份：2025 · DOI：10.1016/j.cllc.2025.04.007 · 被引用次数：7 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics、Colorectal Cancer Treatments and Studies

Background TP53 co-mutations are closely associated with poor outcomes in patients with EGFR -mutant non-small cell lung cancer (NSCLC). Our study aimed to explore whether TP53 co-mutations affect survival and response to EGFR tyrosine kinase inhibitors (TKIs) in patients with different EGFR subtypes. Patients and Methods We retrospectively analyzed 240 NSCLC with EGFR mutation (MT) from the First Affiliated Hospital of Sun Yat-sen University. The effects of TP53 co-mutations on the response to EGFR TKIs were evaluated in EGFR -mutant patients. Results Among various EGFR -mutant subtypes, patients with EGFR L858R / TP53 MT exhibited significantly worse progression-free survival (PFS) than those without TP53 co-mutations (7.9 months vs. 19.8 months, HR=1.53, 95% CI: 1.03-2.28, P = .032), whereas a similar trend did not reappear in subgroups of EGFR 19 del ( P = .730) and EGFR others ( P = .495). Specifically, patients with EGFR L858R /TP53 MT who were treated with second-generation TKIs exhibited worse PFS than those without TP53 co-mutations. TP53 co-mutations were identified as the only independent risk factor for PFS by multivariate analysis. Moreover, TP53 co-mutations mediated the acquisition of resistance in patients harboring EGFR L858R , and concomitant mutations in additional tumor suppressor genes ( TSGs ) ( RB1, NF1, ARID1A , and BRCA1 ) represented a subgroup characterized by an aggressive disease phenotype with worse PFS. Conclusion TP53 co-mutations are associate...