Abstract 1716P
Background
Lung cancer is one of the deadliest cancers worldwide. It can be divided into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Cytochrome P450 Family 4 Subfamily B Member 1 (CYP4B1) is primarily expressed in the lung. We have previously shown that higher CPY4B1 expression is correlated with better survival and a less immunosuppressive microenvironment in LUAD. However, the role of CYP4B1 in LUSC is still unknown. Thus, we analyzed the prognostic value of CYP4B1 and its association with the tumor immune microenvironment.
Methods
A retrospective study was conducted based on the level-3 data in the Cancer Genome Atlas (TCGA)-LUSC (n=501). We used GEPIA2 to study the expression of CYP4B1 in LUSC compared to the normal lung tissue. We assessed the effect of CYP4B1 expression on the overall survival (OS) in LUSC using the Kaplan Meier plotter. We studied the tumor immune microenvironment using TIMER 2.0. To further understand the underlying function of CYP4B1. Enrichment analysis of function and signaling pathways of differentially co-expressed genes were performed by gene ontology (GO) and The Kyoto Encyclopedia of Genes and Genomics (KEGG) analysis using LinkedOmics.
Results
CYP4B1 was downregulated in LUSC compered to normal lung tissues (P < 0.001). Higher CYP4B1 expression correlated with worse OS in LUSC patients (HR: 1.35, 95% CI: 1.03 – 1.78, P = 0.029). CYP4B1 expression was positively correlated with the infiltration of CD8+ cells (spearman’s ρ = 0.147, P < 0.001), Treg cells (spearman’s ρ = 0.107, P < 0.001) and M2 macrophage (spearman’s ρ = 0.335, P < 0.001), but negatively with myeloid-derived suppressor cells (MDSC) (ρ = -0.396, P < 0.001). GO analysis for CYP4B1 co-expressed genes indicated a molecular function role in single-stranded DNA binding and damaged DNA binding and biological process in protein activation cascade and acute inflammatory response with a cellular component in the endosome lumen.
Conclusions
Unlike LUAD, CYP4B1 expression is associated with worse OS in LUSC. This might be due to the infiltration of Tregs and M2 cells even though there were also higher CD8+ cells and lower MDSC. Thus, CYP4B1 might serve as an important predictive and prognostic biomarker in patients treated with immunotherapy.
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.