Coupled immune stratification and identification of therapeutic candidates in patients with lung adenocarcinoma.

ABSTRACT

In recent years, personalized cancer immunotherapy, especially stratification-driven precision treatments have gained significant traction. However, due to the heterogeneity in clinical cohorts, the uncombined analysis of stratification/therapeutics may lead to confusion in determining ideal therapeutic options. We report that the coupled immune stratification and drug repurposing could facilitate identification of therapeutic candidates in patients with lung adenocarcinoma (LUAD). First, we categorized the patients into four groups based on immune gene profiling, associated with distinct molecular characteristics and clinical outcomes. Then, the weighted gene co-expression network analysis (WGCNA) algorithm was used to identify co-expression modules of each groups. We focused on C3 group which is characterized by low immune infiltration (cold tumor) and wild-type EGFR, posing a significant challenge for treatment of LUAD. Five drug candidates against the C3 status were identified which have potential dual functions to correct aberrant immune microenvironment and also halt tumorigenesis. Furthermore, their steady binding affinity against the targets was verified through molecular docking analysis. In sum, our findings suggest that such coupled analysis could be a promising methodology for identification and exploration of therapeutic candidates in the practice of personalized immunotherapy.