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

Cancer Medicine

Tao Mao¹  Ting Liu¹  Zibin Tian¹  Tianyu Fan²  Yi Wan²  Bei Zhang²  Li Zhang²  Bin Wang³  Xin Wang⁴  Zheng Gong⁵  Zugui Zhang⁶ 

[1] Department of Gastroenterology The Affiliated Hospital of Qingdao University Qingdao Shandong Province China;Department of Immunology School of Basic Medicine Qingdao University Qingdao Shandong Province China;Department of Specialty Medicine School of Basic Medicine Qingdao University Qingdao Shandong Province China;School of Stomatology Qingdao University Qingdao Shandong Province China;Sino‐Cellbiomed Institutes of Medical Cell & Pharmaceutical Proteins Qingdao University Qingdao Shandong Province China;Value InstituteChristiana Care Health System Newark DE USA;

关键词: CCR2;    lung adenocarcinoma;    prognosis;    TCGA;    tumor‐infiltrating immune cells;   

DOI  :  10.1002/cam4.3931

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown