CCR2 and PTPRC are regulators of tumor microenvironment and potential prognostic biomarkers of lung adenocarcinoma

Abstract

Background: Tumor microenvironment (TME) plays an essential role in lung adenocarcinoma (LUAD) development and metastasis. With the development of TME research, it has been proved that differences in tumor-infiltrating immune cells (TICs) and gene expression profile are related to the prognosis of cancer.The aim of our study was to identify key genes affecting immune state in TME of LUAD. Methods:The RNA-seq data and clinical characteristics of 594 LUAD patients were downloaded from the TCGA database. ImmuneScore, StromalScore and ESTIMATEScore of each LUAD sample were calculated using ESTIMATE algorithm. Based on the median of different scores, LUAD samples were divided into high and low score groups. Differentially expressed genes (DEGs) between groups were obtained, and univariate Cox regression analysis and protein-protein interaction (PPI) network were used to screen the shared DEGs generating in the intersection analysis. Finally, the CIBORSORT algorithm was performed to calculate the relative contents of TICs for each LUAD sample, and the correlation analysis between TICs and key genes was used to determine the influence of key genes to the TME.Results: In the presented study, we found that three different scores were positively correlated with the prognosis of LUAD patients, and correlation analysis showed the different scores were closely related to tumor progression and metastasis. After performing the intersection analysis, a total of 585 up-regulated and 107 down-regulated DEGs between the high and low score groups were obtained, all of which were enriched in immune-related functions. Having used univariate COX regression analysis and PPI network, the key genes, CCR2 and PTPRC, affecting the immune status of TME and the prognosis of LUAD were acquired.Analysis based on the CIBERSORT algorithm suggested that CCR2 and PTPRC were correlated with a variety of TICs, and closely related to the clinical characteristics of the LUAD patients.Conclusions: Our research showed that CCR2 and PTPRC may be potential prognostic markers in LUAD, which may affect the function of γδT cells and other immune cells by participating in the regulation of TME immune state.

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“…Quan et al identified BRWD1 and its corresponding biological processes involved in the development of AD by constructing an AD protein interaction network [31]. PTPRC was identified as Parkinson's disease biomarker [32] and in lung adenocarcinoma, latent tuberculosis, and ovarian cancer, PTPRC served as a key hub gene and was highly associated with disease [33][34][35]. These results suggest that the constructed LASSO model could provide valuable clues for researchers Computational and Mathematical Methods in Medicine to identify key AD-related diagnostic biomarkers.…”

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“…PTPRC, also known as CD45, expressed on nucleated cells of the hematopoietic system, is an essential regulator of B- and T-cell receptor signaling ( 21 , 22 ). In recent years, many studies have reported that CD45 had promoted the development of diabetes and its metabolic syndrome.…”

“…Further analysis demonstrated that PTPRC, CD53, IRF8, IL10RA, and LAPTM5 perhaps have the essential functions in molecular mechanisms of DN. PTPRC, also known as CD45, expressed on nucleated cells of the hematopoietic system, is an essential regulator of B-and Tcell receptor signaling (21,22). In recent years, many studies have reported that CD45 had promoted the development of diabetes and its metabolic syndrome.…”

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