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

Sep 24, 2026

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Pan-cancer analysis was performed to characterize cell cycle signaling and clarify how cell cycle–related genes influence non-small cell lung cancer (NSCLC). Cluster analysis identified three NSCLC subtypes with distinct immune microenvironments, metabolic remodeling patterns, and cell death pathway profiles. Prognostic associations differed between lung adenocarcinoma and lung squamous cell carcinoma. ZWINT expression correlated with LUAD outcome and showed higher levels in NSCLC than in adjacent tissues, with EMT activation proposed as a potential mechanism for tumor progression.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Background

Methods

Results

Conclusion

Keywords

TYPE Original Research PUBLISHED 06 April 2023 DOI 10.3389/fendo.2023.1147366 OPEN ACCESS EDITED BY Chenyu Sun, AMITA Health, United States REVIEWED BY Qun Zhao, Fourth Hospital of Hebei Medical University, China Mubashir Ayaz Ahmed, AMITA Health St Joseph Hospital, United States Xiuzhi Jia, Zhejiang University, China *CORRESPONDENCE Shijun Li [lishijun@dmu.edu.cn](lishijun@dmu.edu.cn) SPECIALTY SECTION This article was submitted to Cancer Endocrinology, a section of the journal Frontiers in Endocrinology RECEIVED 18 January 2023 ACCEPTED 08 March 2023 PUBLISHED 06 April 2023 CITATION Cao S, Xiao S, Zhang J and Li S (2023) 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. Front. Endocrinol. 14:1147366 . doi: 10.3389/fendo.2023.1147366 COPYRIGHT © 2023 Cao, Xiao, Zhang and Li. 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. 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 Shengji Cao 1, Sitong Xiao 2, Jingyang Zhang 1 and Shijun Li 1* 1 Department of Clinical Laboratory Medicine, First Afﬁliated Hospital of Dalian Medical University, Dalian, China, 2 Department of Clinical Laboratory Medicine, The Third People’s Hospital of Yuhang District, Hangzhou, China 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. Frontiers in Endocrinology 01 [frontiersin.org](frontiersin.org) Conclusion: This

FAQs

What was the main goal of the study in NSCLC?

To evaluate cell cycle–related genes in NSCLC and determine how they relate to tumor immune microenvironment features, cell death pathways, and metabolic reprogramming, including identifying molecular subtypes linked to prognosis.

How were NSCLC subtypes identified?

The study used cluster analysis based on cell cycle signaling to reveal three potential NSCLC subtypes and then compared immune, metabolic, and cell death differences among them.

What role did ZWINT play in the findings?

ZWINT was significantly associated with prognosis in LUAD, showed higher expression in NSCLC versus paracancerous tissues, and was linked to tumor progression through epithelial-mesenchymal transition (EMT) activation.

Sep 24, 2026

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