Less immune cell infiltration and worse prognosis after immunotherapy for patients with lung adenocarcinoma who harbored STK11 mutation

Abstract

The STK11 mutation defined a special subtype for patients with lung adenocarcinoma. The cBioPortal data platform was applied to analyze STK11 mutation frequency and the relationship between STK11 mutation and immune prognostic markers. The TIMER database was used to analyze the relationship between STK11 mutation and immune cell infiltration. The survival difference for lung adenocarcinoma patients harbored STK11 mutation who received immunotherapy also used the cBioPortal database. The results showed that STK11 mutation co-occurrence more KRAS and KEAP1 mutation and fewer TP53 and EGFR mutation (all, P < 0.05); the patients harbored STK11 mutation had a lower expression of PDL1 (P = 0.002), higher TMB score (P = 0.002), higher proportion of males and smoking history; the patients harbored STK11 mutation had fewer immune cell infiltration including B cell (P < 0.01), CD8+ T cell (P < 0.001), CD4+ T cell (P < 0.001), Macrophage (P < 0.001), Neutrophil (P < 0.001) and Dendritic cell (P < 0.001). Importantly, we found the patients harbored STK11 mutation who received immune checkpoint inhibitors have worse overall survival (OS) with median survival only 6 months. In conclusion, our study demonstrated that STK11 mutation defined a special subtype for lung adenocarcinoma patients with different co-occurrence gene mutation, lower PDL1 expression, fewer immune cell infiltration and worse OS benefit from immune checkpoint inhibitors.

Keywords: Immune checkpoint inhibitors; Lung adenocarcinoma; Prognosis; STK11 mutation.