Yin Dandan, Lu Xiyi, Liang Xiao, Lu Yiting, Xiong Lei, Wu Pingping, Wang Tingting, Chen Jinfei
The Second Hospital of Nanjing, Clinical Teaching Hospital of Medical School, Nanjing University, Nanjing, People's Republic of China.
Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, Jiangsu, People's Republic of China.
Sci Rep. 2025 Feb 17;15(1):5729. doi: 10.1038/s41598-024-74779-6.
This study was conducted to investigate the relationship between STK11 genetic alterations and the outcomes of patients with metastatic EGFR mutant lung cancer. Clinical characteristics and genomic data were downloaded from the cBioPortal database. The information of the case with STK11 mutation was collected from Jiangyin People's Hospital. Univariate and multivariate analyses were performed to distinguish the prognostic differences. Outcomes were analyzed before and after propensity score matching (PSM). A patient with STK11 mutation was insensitive to osimertinib and had an extremely poor prognosis. Further analysis showed that STK11 mutations had a strong mutual exclusion with EGFR mutations. A total of 960 patients with metastatic EGFR mutant lung adenocarcinoma were enrolled in the prognostic analysis. STK11 alternation was a significant predictor of worse outcomes in univariate or multivariate analyses. After PSM, patients with STK11 alternations still exhibited poor prognoses. Cell culture experiments also showed that the loss of STK11 could contribute to the resistance of osimertinib. Functionally, STK11 mutation was positively associated with metabolic signaling pathways and immune infiltrates negatively. Through drug screening, trametinib was identified to sensitize osimertinib in the STK11-deficient cell. This study found that STK11 genetic alterations portend a worse prognosis for patients with metastatic EGFR mutant lung cancer and led to osimertinib resistance potentially. MEK inhibitors could sensitize osimertinib in the STK11-deficient cell.
本研究旨在探讨STK11基因改变与转移性EGFR突变肺癌患者预后之间的关系。临床特征和基因组数据从cBioPortal数据库下载。STK11突变病例的信息从江阴人民医院收集。进行单因素和多因素分析以区分预后差异。在倾向评分匹配（PSM）前后分析预后。STK11突变患者对奥希替尼不敏感且预后极差。进一步分析表明，STK11突变与EGFR突变存在强烈的相互排斥。共有960例转移性EGFR突变肺腺癌患者纳入预后分析。在单因素或多因素分析中，STK11改变是预后较差的显著预测因素。PSM后，STK11改变的患者仍表现出不良预后。细胞培养实验还表明，STK11缺失可导致对奥希替尼的耐药性。在功能上，STK11突变与代谢信号通路呈正相关，与免疫浸润呈负相关。通过药物筛选，发现曲美替尼可使STK11缺陷细胞对奥希替尼敏感。本研究发现，STK11基因改变预示着转移性EGFR突变肺癌患者预后较差，并可能导致奥希替尼耐药。MEK抑制剂可使STK11缺陷细胞对奥希替尼敏感。
