Expression of RASGRP2 in Lung Adenocarcinoma and Its Effect 
on Immune Microenvironment

Abstract

Background and objective Lung cancer still has the highest incidence rate and mortality rate nowadays. In recent years, with the emergence of new drugs and the optimization of treatment mode, especially the clinical application of immunotherapy, the prognosis of lung cancer patients has been improved. However, the benefits of immunotherapy are still limited. Therefore, it is necessary to find new biomarkers to predict the prognosis of lung adenocarcinoma patients and explore its impact on the immune microenvironment. Methods The Cancer Genome Atlas (TCGA) database was used to analyze the gene sequencing and clinical data of patients with lung adenocarcinoma. The distribution of RASGRP2 in lung adenocarcinoma was determined by using the human protein mapping database. The Kaplan-Meier plotter database was used to explore the relationship between the expression of RASGRP2 and the prognosis of patients with lung adenocarcinoma. KEGG and GO gene enrichment analysis was performed in patients with high and low expression of RASGRP2. TCGA database was used to analyze the co-expression genes of RASGRP2 and TIMER database was used to calculate the immune related lymphoid infiltration of RASGRP2 and its coexpression genes. The relationship between RASGRP2 expression and immune checkpoint expression was analyzed by using TIMER 2.0 database. Results We found that RASGRP2 was low expressed in lung adenocarcinoma, and its expression level was related to the prognosis of patients. The high expression of RASGRP2 was involved in the process of hematopoietic cell formation and cell adhesion, and RASGRP2 played an important role in the process of T cell activation. Through TCGA database analysis, ZAP70, TBC1D10C, RASAL3, FGD2, CD37 and ACAP1 were significantly correlated with RASGRP2. The high expression of these genes leaded to the increase of the proportion of CD8+ T cells, memory CD4+ T cells, and the decrease of the proportion of neutrophils and Treg cells. Finally, we found that the expression of RASGRP2 was significantly correlated with the expression of CD274, CTLA4, LAG3 and TIGIT. Conclusion RASGRP2 was abnormally expressed in lung adenocarcinoma and correlated with the infiltration level of immune related cells, which might influence the efficacy of immunotherapy.

Keywords

• lung adenocarcinoma
• immunotherapy
• rasgrp2
• prognosis
• immune microenvironment