NRAS expression is associated with prognosis and tumor immune microenvironment in lung adenocarcinoma

• Published in: Journal of cancer research and clinical oncology 2022-03, Vol.148 (3), p.565-575
• Main Authors: Yan, Yueren, Gao, Zhendong, Han, Han, Zhao, Yue, Zhang, Yang, Ma, Xiangyi, Chen, Haiquan
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma of Lung - immunology; Adenocarcinoma of Lung - metabolism; Adenocarcinoma of Lung - pathology; Adenocarcinoma of Lung - surgery; Aged; Biomarkers; Biomarkers, Tumor - metabolism; Cancer; Cancer Research; CD4 antigen; CD8 antigen; Female; Follow-Up Studies; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene set enrichment analysis; Genomes; GTP Phosphohydrolases - metabolism; Hematology; Humans; Internal Medicine; Leukocytes (neutrophilic); Lung cancer; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Lymph nodes; Lymphocytes B; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Macrophages; Male; Medicine; Medicine & Public Health; Membrane Proteins - metabolism; Microenvironments; Middle Aged; Oncology; Original Article – Cancer Research; Patients; PD-1 protein; PD-L1 protein; Prognosis; Retrospective Studies; Survival Rate; Transcriptomes; Tumor Microenvironment; Tumor-infiltrating lymphocytes
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-021-03842-w

Purpose NRAS plays a pivotal role in progression of various kinds of somatic malignancies; however, the correlation between NRAS and lung adenocarcinoma is less known. We aim to analyze the prognostic value of NRAS expression in lung adenocarcinoma, and explore the relationship between NRAS and tumor immune microenvironment. Methods We obtained the transcriptome profiles and clinical data of LUAD from The Cancer Genome Atlas database and three Genome Expression Omnibus datasets. Specimens from 325 patients with completely resected lung adenocarcinoma were collected for immunohistochemical assays of NRAS, PD-L1, PD-1 and TIM-3. Then, we performed gene set enrichment analysis to investigate cancer-related and immune-related signaling pathways. TIMER algorithms were performed to evaluate tumor immune infiltrating cells and immune-related biomarkers. Results Compared with adjacent non-tumor tissue, NRAS expression was significantly upregulated in LUAD tissue. NRAS expression was significantly correlated with more advanced stage and positive lymph nodes. Kaplan–Meier curves and Cox analysis suggested that high NRAS expression led to a poor prognosis, and could be an independent prognostic factor in LUAD patients. Besides, NRAS expression was positively correlated with CD8+ T cells, macrophages, and neutrophils, and negatively correlated with B cells and CD4+ T cells. The expression level of NRAS was positively correlated with PD-L1, PD-1, and TIM-3 both at RNA and protein level. Conclusions To conclude, we found NRAS is a novel prognostic biomarker in LUAD. Besides, the expression level of NRAS may influence the prognosis of LUAD via various kinds of cancer-related pathways and remodeling TIM.