Cross-talk of Three Molecular Subtypes of Telomere Maintenance Defines Clinical Characteristics and Tumor Microenvironment in Gastric Cancer

Yan, Mengpei; Zhang, Zhijun; Wang, Luyao; Huang, Hongxin; Wang, Jihuan; Zhu, Chengjun; Li, Zheng; Xu, Zekuan

doi:10.7150/jca.92207

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J Cancer 2024; 15(10):3227-3241. doi:10.7150/jca.92207 This issue Cite

Research Paper

Cross-talk of Three Molecular Subtypes of Telomere Maintenance Defines Clinical Characteristics and Tumor Microenvironment in Gastric Cancer

Mengpei Yan^1*, Zhijun Zhang^1*, Luyao Wang^1*, Hongxin Huang^1*, Jihuan Wang¹, Chengjun Zhu¹, Zheng Li^1✉, Zekuan Xu^1,2,3✉

1. Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China.
2. Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China.
3. The Institute of Gastric Cancer, Nanjing Medical University, Nanjing, Jiangsu Province, China.
* These authors contributed equally to this work.

Citation:

Yan M, Zhang Z, Wang L, Huang H, Wang J, Zhu C, Li Z, Xu Z. Cross-talk of Three Molecular Subtypes of Telomere Maintenance Defines Clinical Characteristics and Tumor Microenvironment in Gastric Cancer. J Cancer 2024; 15(10):3227-3241. doi:10.7150/jca.92207. https://www.jcancer.org/v15p3227.htm

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Abstract

Background: Telomere maintenance takes part in the regulation of gastric cancer (GC) pathogenesis and is essential for patients' clinical features. Though the correlation between a single telomere maintenance-related gene and GC has previously been published, comprehensive exploration and systematic analysis remain to be studied. Our study is aimed at determining telomere maintenance-related molecular subtypes and examining their role in GC.

Methods: By analyzing the transcriptome data, we identified three telomere maintenance-associated clusters (TMCs) with heterogeneity in clinical features and tumor microenvironment (TME). Then, we screened five prognostic telomere maintenance-related genes and established corresponding TM scores. Additionally, the expression level and biological function of tubulin beta 6 class V (TUBB6) were validated in GC tissues and cells.

Results: TMC1 was correlated with EMT and TGF-beta pathway and predicted low tumor mutation burden (TMB) as well as bad prognostic outcomes. TMC3 was associated with cell cycle and DNA repair. In terms of TMB and overall survival, TMC3 exhibited opposite results against TMC1. Significant heterogeneity was observed between TMCs. TUBB6 was upregulated and could promote GC proliferation, migration, and invasion.

Conclusion: Altogether, combining bioinformatics and functional experiments, we identified three molecular subtypes based on telomere maintenance-associated genes in GC, which could bring new ideas and novel biomarkers to the clinic.

Keywords: telomere maintenance, gastric cancer, tumor immune infiltration, molecular subtypes, TUBB6

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APA

Yan, M., Zhang, Z., Wang, L., Huang, H., Wang, J., Zhu, C., Li, Z., Xu, Z. (2024). Cross-talk of Three Molecular Subtypes of Telomere Maintenance Defines Clinical Characteristics and Tumor Microenvironment in Gastric Cancer. Journal of Cancer, 15(10), 3227-3241. https://doi.org/10.7150/jca.92207.

ACS

Yan, M.; Zhang, Z.; Wang, L.; Huang, H.; Wang, J.; Zhu, C.; Li, Z.; Xu, Z. Cross-talk of Three Molecular Subtypes of Telomere Maintenance Defines Clinical Characteristics and Tumor Microenvironment in Gastric Cancer. J. Cancer 2024, 15 (10), 3227-3241. DOI: 10.7150/jca.92207.

NLM

CSE

Yan M, Zhang Z, Wang L, Huang H, Wang J, Zhu C, Li Z, Xu Z. 2024. Cross-talk of Three Molecular Subtypes of Telomere Maintenance Defines Clinical Characteristics and Tumor Microenvironment in Gastric Cancer. J Cancer. 15(10):3227-3241.

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