Stratification of non-small cell lung adenocarcinoma patients with EGFR actionable mutations based on drug-resistant stem cell genes

EGFR-TKIs were used in NSCLC patients with actionable EGFR mutations and pro-long prognosis. However, most patients treated with EGFR-TKIs developed resis-tance within around one year. This suggests that residual EGFR-TKIs resistant cells may eventually lead to relapse. Predicting resistance risk in patients will facilitate individualized management. Herein, we built an EGFR-TKIs resistance prediction (R-index) model and validate in cell line, mice, and cohort. We found significantly higher R-index value in resistant cell lines, mice models and relapsed patients. Patients with an elevated R-index had significantly shorter relapse time. We also found that the glycolysis pathway and the KRAS upregulation pathway were related to EGFR-TKIs resistance. MDSC is a significant immunosuppression factor in the resistant microenvironment. Our model provides an executable method for assessing patient resistance status based on transcriptional reprog-ramming and may contribute to the clinical translation of patient individual man-agement and the study of unclear resistance mechanisms.