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Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming

BACKGROUND: The genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cel...

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Autores principales: Cao, Shengji, Xiao, Sitong, Zhang, Jingyang, Li, Shijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117961/
https://www.ncbi.nlm.nih.gov/pubmed/37091844
http://dx.doi.org/10.3389/fendo.2023.1147366
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author Cao, Shengji
Xiao, Sitong
Zhang, Jingyang
Li, Shijun
author_facet Cao, Shengji
Xiao, Sitong
Zhang, Jingyang
Li, Shijun
author_sort Cao, Shengji
collection PubMed
description BACKGROUND: The genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cell cycle in all types of cancers, especially NSCLC. METHODS: This study constituted the first pan-cancer landscape of cell cycle signaling. Cluster analysis based on cell cycle signaling was conducted to identify the potential molecular heterogeneity of NSCLC. Further, the discrepancies in the tumor immune microenvironment, metabolic remodeling, and cell death among the three clusters were investigated. Immunohistochemistry was performed to validate the protein levels of the ZWINT gene and examine its relationship with the clinical characteristics. Bioinformatics analyses and experimental validation of the ZWINT gene were also conducted. RESULTS: First, pan-cancer analysis provided an overview of cell cycle signaling and highlighted its crucial role in cancer. A majority of cell cycle regulators play risk roles in lung adenocarcinoma (LUAD); however, some cell cycle genes play protective roles in lung squamous cell carcinoma (LUSC). Cluster analysis revealed three potential subtypes for patients with NSCLC. LUAD patients with high cell cycle activities were associated with worse prognosis; while, LUSC patients with high cell cycle activities were associated with a longer survival time. Moreover, the above three subtypes of NSCLC exhibited distinct immune microenvironments, metabolic remodeling, and cell death pathways. ZWINT, a member of the cell signaling pathway, was observed to be significantly associated with the prognosis of LUAD patients. A series of experiments verified the higher expression levels of ZWINT in NSCLC compared to those in paracancerous tissues. The activation of epithelial-mesenchymal transition (EMT) induced by ZWINT might be responsible for tumor progression. CONCLUSION: This study revealed the regulatory function of the cell cycle genes in NSCLC, and the molecular classification based on cell cycle-associated genes could evaluate the different prognoses of patients with NSCLC. ZWINT expression was found to be significantly upregulated in NSCLC tissues, which might promote tumor progression via activation of the EMT pathway.
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spelling pubmed-101179612023-04-21 Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming Cao, Shengji Xiao, Sitong Zhang, Jingyang Li, Shijun Front Endocrinol (Lausanne) Endocrinology BACKGROUND: The genes related to the cell cycle progression could be considered the key factors in human cancers. However, the genes involved in cell cycle regulation in non-small cell lung cancer (NSCLC) have not yet been reported. Therefore, it is necessary to evaluate the genes related to the cell cycle in all types of cancers, especially NSCLC. METHODS: This study constituted the first pan-cancer landscape of cell cycle signaling. Cluster analysis based on cell cycle signaling was conducted to identify the potential molecular heterogeneity of NSCLC. Further, the discrepancies in the tumor immune microenvironment, metabolic remodeling, and cell death among the three clusters were investigated. Immunohistochemistry was performed to validate the protein levels of the ZWINT gene and examine its relationship with the clinical characteristics. Bioinformatics analyses and experimental validation of the ZWINT gene were also conducted. RESULTS: First, pan-cancer analysis provided an overview of cell cycle signaling and highlighted its crucial role in cancer. A majority of cell cycle regulators play risk roles in lung adenocarcinoma (LUAD); however, some cell cycle genes play protective roles in lung squamous cell carcinoma (LUSC). Cluster analysis revealed three potential subtypes for patients with NSCLC. LUAD patients with high cell cycle activities were associated with worse prognosis; while, LUSC patients with high cell cycle activities were associated with a longer survival time. Moreover, the above three subtypes of NSCLC exhibited distinct immune microenvironments, metabolic remodeling, and cell death pathways. ZWINT, a member of the cell signaling pathway, was observed to be significantly associated with the prognosis of LUAD patients. A series of experiments verified the higher expression levels of ZWINT in NSCLC compared to those in paracancerous tissues. The activation of epithelial-mesenchymal transition (EMT) induced by ZWINT might be responsible for tumor progression. CONCLUSION: This study revealed the regulatory function of the cell cycle genes in NSCLC, and the molecular classification based on cell cycle-associated genes could evaluate the different prognoses of patients with NSCLC. ZWINT expression was found to be significantly upregulated in NSCLC tissues, which might promote tumor progression via activation of the EMT pathway. Frontiers Media S.A. 2023-04-06 /pmc/articles/PMC10117961/ /pubmed/37091844 http://dx.doi.org/10.3389/fendo.2023.1147366 Text en Copyright © 2023 Cao, Xiao, Zhang and Li 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 Endocrinology
Cao, Shengji
Xiao, Sitong
Zhang, Jingyang
Li, Shijun
Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming
title Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming
title_full Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming
title_fullStr Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming
title_full_unstemmed Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming
title_short Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming
title_sort identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117961/
https://www.ncbi.nlm.nih.gov/pubmed/37091844
http://dx.doi.org/10.3389/fendo.2023.1147366
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