Abstract 1202P
Background
Lung adenocarcinomas (LUAD) harboring epidermal growth factor receptor (EGFR) mutations generally are unable to benefit from immune checkpoint inhibitors (ICIs), due to an immunosuppressive tumour microenvironment (TME) and a lower tumor mutation burden (TMB). Currently, there has been no gene signature that can comprehensively evaluate the TME and predict the prognosis of EGFR mutant LUAD patients.
Methods
using EGFR mutations and mRNA expression data of lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database.
Results
We screened 396 the differential immune-related genes with prognostic value between the high and low immune score group in 80 patients with EGFR-mutated samples. Top GO terms were significantly enriched in biological functions related to T cell differentiation, immune response, cell cycle and cell proliferation. In addition, KEGG pathway enrichment analysis mainly focused on Cell cycle, Cell adhesion molecules and Cytokine-cytokine receptor interaction. We also compared the TMB profiles based on different immune score groups. TMB score of the low immune score group was higher than that of the high immune score group and disparities could be found in these mutant genes between the high and low immune score group. We identified a three-gene signature (BTLA, BUB1B and CENPE) and constructed risk model by LASSO Cox regression model.The three-gene signature could well identify at-risk patients of EGFR-mutant LUAD patients in the training and validating set, and the high-risk patients were related to short overall survival. The univariate and multivariate Cox proportional hazard regression analyses showed that the three-gene signature was an independent risk factor for prognosis. ROC curves confirmed the robust prognostic value of the three-gene signature in the training and validating set.
Conclusions
the three-gene signature closely related to immunosuppressive TME could predict risk prognosis of patients in EGFR mutant LUAD.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Haiyong Wang.
Funding
Special funds for Taishan Scholars Project (Grant no. tsqn201812149), Academic promotion programme of Shandong First Medical University (2019RC004).
Disclosure
All authors have declared no conflicts of interest.