Prognostic value of CCR2 as an immune indicator in lung adenocarcinoma: A study based on tumor-infiltrating immune cell analysis.

Abstract

BACKGROUND:

Prognostic indicators in lung adenocarcinoma (LUAD) have been seeking under database analysis, and remarkable advance is on the way.

METHODS:

This study calculated the scores of stromal and immune components of the tumor microenvironment (TME) in 551 LUAD samples using the ESTIMATE algorithm on The Cancer Genome Atlas (TCGA) database. R package ''limma'' was used to selected differentially expressed genes (DEG). We have analyzed the DEGs by means of Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments. The protein-protein network, univariate Cox analysis, and Lasso regression analysis were performed to selected survival-related genes. Gene Set Enrichment Analysis (GSEA) represented the enriched pathway of CC chemokine receptor 2 (CCR2). The ratios of immune cells in the TME of each LUAD sample were obtained using the R package "limma" and CIBERSORT algorithm in R 4.0.2.

RESULTS:

The ImmuneScore was positively correlated with prognosis regarding survival rate, T classification of TNM stages, and clinicopathological staging characteristics. GO and KEGG enrichments showed DEGs were associated with immune-related activities. Three genes of LUAD were selected from the PPI network and Cox proportional hazards regression analysis. CCR2 was the most survival correlated gene by Lasso regression analysis. GSEA results showed that C2 kegg gene sets in the CCR2 high-expression group were mainly enriched in the B cell or T cell receptor signaling pathway and natural killer cell-mediated cytotoxicity. Correlation of CCR2 expression with prognosis was conducted, implicating a positive correlation with the prognosis of survival rate and M classification, negative correlation with the prognosis of T and N classifications. The correlation between CCR2 and tumor-infiltrating immune cells (TICs) was analyzed, and 14 kinds of TICs were found closely correlated with CCR2 expression through difference analysis.

CONCLUSION:

Therefore, CCR2 has prognostic value as an immune indicator in LUAD.

• Authors: Yi Wan, Xin Wang, Ting Liu, Tianyu Fan, Zugui Zhang, Bin Wang, Bei Zhang, Zibin Tian, Tao Mao, Zheng Gong, Li Zhang
• Journal: Cancer medicine (Cancer Med) Vol. 10 Issue 12 Pg. 4150-4163 (06 2021) ISSN: 2045-7634 [Electronic] United States
• PMID: 33949150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• CCR2 protein, human
• Receptors, Antigen, B-Cell
• Receptors, Antigen, T-Cell
• Receptors, CCR2

Topics

• Adenocarcinoma of Lung (genetics, immunology, mortality, pathology)
• Aged
• Algorithms
• Databases, Genetic
• Female
• Gene Expression
• Gene Ontology
• Humans
• Killer Cells, Natural (immunology)
• Lung Neoplasms (genetics, immunology, mortality, pathology)
• Lymphocytes, Tumor-Infiltrating
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Receptors, Antigen, B-Cell (genetics)
• Receptors, Antigen, T-Cell (genetics)
• Receptors, CCR2 (genetics)
• Regression Analysis
• Survival Rate
• Tumor Microenvironment (genetics, immunology)