Data Sheet 1_Integrative bioinformatics screening of a M2 macrophage-associated gene signature for osimertinib resistance.pdf

Survival analysis was conducted in the EGFR-mutant TCGA cohort. In vitro cell experiments were further performed for functional validation.</p>Results<p>Single-cell RNA sequencing firstly revealed an increased proportion of M2 macrophages in the OR group, and M2 macrophage-specific DEGs were identified between OR and non-OR groups. A total of seven MORGs were obtained by intersecting DEGs and OR-related module genes.

A 7-gene signature was successfully established via machine learning. Survival analysis demonstrated that RRBP1 showed the strongest association with overall survival and was selected for further investigation. In vitro experiments confirmed that RRBP1 was significantly upregulated in the H1975OR cells.

Knockdown of RRBP1 reduced cell viability and migration, lowered the IC50 of osimertinib, and increased the expression of ER stress markers such as GRP78 and CHOP.</p>Conclusion<p>In summary, our study identified a 7-MORGs signature for OR, among which RRBP1 may be a candidate regulator for OR.</p>