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CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma
BACKGROUND: The tumor microenvironment plays an important role in the occurrence and development of tumors. However, there are gaps in understanding the molecular and cellular interactions between tumor cells and the immune tumor microenvironment (TME). The aim of this study was to identify a novel...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096117/ https://www.ncbi.nlm.nih.gov/pubmed/35574409 http://dx.doi.org/10.3389/fonc.2022.822849 |
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author | Zhu, Ningning Yang, Yueyang Wang, Haitong Tang, Peng Zhang, Hongdian Sun, Haiyan Gong, Lei Yu, Zhentao |
author_facet | Zhu, Ningning Yang, Yueyang Wang, Haitong Tang, Peng Zhang, Hongdian Sun, Haiyan Gong, Lei Yu, Zhentao |
author_sort | Zhu, Ningning |
collection | PubMed |
description | BACKGROUND: The tumor microenvironment plays an important role in the occurrence and development of tumors. However, there are gaps in understanding the molecular and cellular interactions between tumor cells and the immune tumor microenvironment (TME). The aim of this study was to identify a novel gene that played an important role in the tumor microenvironment of lung adenocarcinoma (LUAD). METHODS: The gene expression profile and clinical data for LUAD were downloaded from TCGA database. First, we used the ESTIMATE algorithm to evaluate the immune and stromal scores accordingly. Also, we analyzed differentially expressed immune-related genes (IRGs) in the high and low immune/stromal score groups. Then, we used the protein–protein interaction network (PPI network) and a univariate Cox regression analysis to identify the hub gene. After that, we analyzed the relationship between CSF2RB expression and TNM stage/prognosis. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathway regulated by CSF2RB and the Pearson correlation analysis method was used to analyze the correlation between the CSF2RB and immune cells. Finally, we used Western blot, real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC) to validate CSF2RB expression in cancer and para-cancerous tissues. RESULTS: We identified that CSF2RB played an important role in the tumor microenvironment of LUAD. The expression of CSF2RB in tumor tissues was lower than that in normal tissues. Furthermore, the Kaplan–Meier plotter showed that a low CSF2RB expression was associated with poor survival and multivariate COX regression analysis revealed that the CSF2RB gene was an independent risk factor for prognosis, independent of whether patients received chemotherapy or radiotherapy. More importantly, a high expression of CSF2RB was related to early T, N, and clinical stages. GSEA analysis revealed that CSF2RB associated with diverse immune-related pathways, including T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and B-cell receptor signaling pathway. CSF2RB expression levels were also positively related with the levels of infiltrating CD4+ T cells, macrophages, NK cells, and monocytes in LUAD. Finally, tumor tissues from LUAD patients were used for the assessment of CSF2RB expression. It was significantly lower in tumor sites than in adjacent normal tissues, which was consistent with data analysis. CONCLUSION: CSF2RB effectively predicted the prognosis of patients with lung adenocarcinoma which could also be a potential target for cancer treatment and prevention. However, further studies are required to elucidate the function and regulatory mechanisms of CSF2RB and to develop some novel treatment strategies. |
format | Online Article Text |
id | pubmed-9096117 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90961172022-05-13 CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma Zhu, Ningning Yang, Yueyang Wang, Haitong Tang, Peng Zhang, Hongdian Sun, Haiyan Gong, Lei Yu, Zhentao Front Oncol Oncology BACKGROUND: The tumor microenvironment plays an important role in the occurrence and development of tumors. However, there are gaps in understanding the molecular and cellular interactions between tumor cells and the immune tumor microenvironment (TME). The aim of this study was to identify a novel gene that played an important role in the tumor microenvironment of lung adenocarcinoma (LUAD). METHODS: The gene expression profile and clinical data for LUAD were downloaded from TCGA database. First, we used the ESTIMATE algorithm to evaluate the immune and stromal scores accordingly. Also, we analyzed differentially expressed immune-related genes (IRGs) in the high and low immune/stromal score groups. Then, we used the protein–protein interaction network (PPI network) and a univariate Cox regression analysis to identify the hub gene. After that, we analyzed the relationship between CSF2RB expression and TNM stage/prognosis. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathway regulated by CSF2RB and the Pearson correlation analysis method was used to analyze the correlation between the CSF2RB and immune cells. Finally, we used Western blot, real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC) to validate CSF2RB expression in cancer and para-cancerous tissues. RESULTS: We identified that CSF2RB played an important role in the tumor microenvironment of LUAD. The expression of CSF2RB in tumor tissues was lower than that in normal tissues. Furthermore, the Kaplan–Meier plotter showed that a low CSF2RB expression was associated with poor survival and multivariate COX regression analysis revealed that the CSF2RB gene was an independent risk factor for prognosis, independent of whether patients received chemotherapy or radiotherapy. More importantly, a high expression of CSF2RB was related to early T, N, and clinical stages. GSEA analysis revealed that CSF2RB associated with diverse immune-related pathways, including T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and B-cell receptor signaling pathway. CSF2RB expression levels were also positively related with the levels of infiltrating CD4+ T cells, macrophages, NK cells, and monocytes in LUAD. Finally, tumor tissues from LUAD patients were used for the assessment of CSF2RB expression. It was significantly lower in tumor sites than in adjacent normal tissues, which was consistent with data analysis. CONCLUSION: CSF2RB effectively predicted the prognosis of patients with lung adenocarcinoma which could also be a potential target for cancer treatment and prevention. However, further studies are required to elucidate the function and regulatory mechanisms of CSF2RB and to develop some novel treatment strategies. Frontiers Media S.A. 2022-04-28 /pmc/articles/PMC9096117/ /pubmed/35574409 http://dx.doi.org/10.3389/fonc.2022.822849 Text en Copyright © 2022 Zhu, Yang, Wang, Tang, Zhang, Sun, Gong and Yu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Zhu, Ningning Yang, Yueyang Wang, Haitong Tang, Peng Zhang, Hongdian Sun, Haiyan Gong, Lei Yu, Zhentao CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma |
title | CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma |
title_full | CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma |
title_fullStr | CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma |
title_full_unstemmed | CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma |
title_short | CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma |
title_sort | csf2rb is a unique biomarker and correlated with immune infiltrates in lung adenocarcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096117/ https://www.ncbi.nlm.nih.gov/pubmed/35574409 http://dx.doi.org/10.3389/fonc.2022.822849 |
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