Background: 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.
Conclusions: RASGRP2 was abnormally expressed in lung adenocarcinoma and correlated with the infiltration level of immune related cells, which might influence the efficacy of immunotherapy.
【中文题目：RASGRP2在肺腺癌中的表达 及对免疫微环境的影响】 【中文摘要：背景与目的 肺癌是全球发病率和死亡率的居高不下的恶性肿瘤。近年来，随着新型药物的出现和治疗模式的优化，特别是免疫治疗在临床的应用，肺癌患者的预后已经有了一定的改善。但免疫治疗获益的患者仍然有限，因此我们想要寻找新的生物标志物用于预测肺腺癌患者的预后并探索其对免疫微环境的影响。方法 使用癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库下载肺腺癌患者的测序结果及临床资料。利用人类蛋白质图谱数据库明确RASGRP2在肺腺癌中分布情况，使用Kaplan-Meier Plotter数据库探索RASGRP2表达情况与肺腺癌患者预后之间的联系。对RASGRP2高低表达患者进行KEGG及GO基因富集分析。使用TCGA数据库分析RASGRP2共表达基因并使用TIMER数据库计算RASGRP2及其共表达基因的免疫相关淋巴浸润情况。最后使用TIMER 2.0数据库分析RASGRP2表达量与免疫检查点表达的联系。结果 RASGRP2在肺腺癌中低表达，与患者预后密切相关。RASGRP2高表达参与造血细胞形成及细胞黏附，且在T细胞活化进程中有着重要作用。通过TCGA数据库分析发现ZAP70、TBC1D10C、RASAL3、FGD2、CD37、ACAP1与RASGRP2显著相关。以上基因高表达会引起CD8+ T细胞、记忆CD4+ T细胞比例升高以及中性粒细胞和Treg细胞比例降低。最后，我们发现RASGRP2表达量与常见免疫检查点CD274、CTLA4、LAG3、TIGIT等表达量显著相关。结论 RASGRP2在肺腺癌中异常表达且影响免疫相关细胞浸润水平，可能会影响免疫治疗疗效。 】 【中文关键词：肺腺癌；免疫治疗；RASGRP2；预后；免疫微环境】.
Keywords: Immune microenvironment; Immunotherapy; Lung adenocarcinoma; Prognosis; RASGRP2.