Abstract 1720P
Background
Lung adenocarcinoma (LUAD) is one of the deadliest cancers worldwide. Extensive efforts are made to search for new biomarkers to screen for immunotherapy candidates and predict the prognosis. The vasoactive intestinal peptide receptor-1 (VIPR1) has substantial but contradicting effects among different cancers. Herein, we analyzed the association of VIPR1 with immune inhibitory components to understand its immune landscape.
Methods
Gene expression profiles were retrieved from The Cancer Genomic Atlas Lung Adenocarcinoma cohort (TCGA - LAUD) (n = 567). We used the TIMER 2.0 for immune inhibitory cell infiltrates analysis. Tumor mutational burden (TMB) was measured using the cBioPortal tool. The enrichment analysis of function and signaling pathways of DEGs in LUAD were done by gene ontology (GO) using Enrichr.
Results
VIPR1 is differentially expressed in LUAD tissues (P < 0.00). High VIPR1 expression had favorable overall survival prognostic value in LUAD patients (HR: 0.67, 95% CI: 0.50 – 0.91, P = 0.024). VIPR1 expression was negatively correlated with the infiltration of myeloid-derived suppressor cells (MDSC) and cancer-associated fibroblasts (spearman’s ρ = -0.488, P < 0.001, ρ = -0.103, P < 0.001, respectively), but positively with macrophage M2 cells (ρ = 0.193, P < 0.001). Moreover, survival analysis based on VIPR1 expression and MDSC levels revealed a better OS group identified by low VIPR1 expression and low MDSC levels after adjustment for age, stage, and purity. In terms of immune checkpoint genes expression, VIPR1 expression was directly correlated with CTLA-4, PD-1, PD-L1, VSIR, and LAG-3 (ρ > 0.2, Q value < 0.05). TMB count was inversely associated with VIPR1 expression (ρ = -0.17, P < 0.001). GO analysis showed that genes co-expressed with VIPR1 were mainly in the nuclear envelope lumen, and participated in biological processes of icosanoid metabolism by molecular function such as SH3 domain binding.
Conclusions
We found that VIPR1 expression is a useful marker of immunosuppression in LUAD patients and could predict the response to immunotherapy. Our results suggested that VIPR1 is a favorable prognostic marker, which could be explained by low MDSC. Further studies are needed for a better understanding of the VIPR1 value in LAUD.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.