STK11 genetic alterations in metastatic EGFR mutant lung cancer

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.