Identification and validation of biomarkers associated with mitotic catastrophe in high-altitude hypoxia
- 1Traditional Chinese Medicine Department, The General Hospital of Western Theater Command PLA, Chengdu, China
Abstract
Background: High-altitude hypoxia (HAH) can cause adverse reactions, such as tinnitus and barotrauma, but the role of mitotic catastrophe (MC) in HAH remains unreported. This study investigated MC-associated biomarkers in HAH.
Methods: HAH-related datasets and MC-related genes (MC-RGs) were retrieved from public databases. Differentially expressed genes (DEGs) between the HAH and control groups were screened, and overlapping genes between DEGs and MC-RGs were defined as candidates. Biomarkers were identified using three machine learning methods, receiver operating characteristic curve analysis, and expression validation. A nomogram was constructed for diagnostic assessment. Functional enrichment, immune infiltration, regulatory network, and drug prediction analyses were performed, with biomarker expression verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Results: DIAPH1 and MDM4 were confirmed as MC-associated biomarkers in HAH, and the nomogram displayed excellent diagnostic ability (area under the curve = 0.929). These biomarkers were coenriched in pathways such as oxidative phosphorylation. DIAPH1 was positively correlated with the infiltration of resting NK cells, whereas MDM4 was negatively correlated with that of M2 macrophages. A transcription factor–mRNA–miRNA network was established, with USF2 and GATA2 jointly targeting both biomarkers. Drugs such as rescinnamine targeted MDM4. RT-qPCR verified that USF2 and GATA2 were significantly downregulated in HAH (both P < 0.01), consistent with the bioinformatics results.
Conclusions: DIAPH1 and MDM4 are valid MC-associated biomarkers for HAH. This study provides novel insights into HAH prevention and treatment.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s41065-026-00692-9.
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BibTeX
@article{zhao2026identification,
title = {{Identification and validation of biomarkers associated with mitotic catastrophe in high-altitude hypoxia}},
author = {Wenwen Zhao and Defang Liu and Ting Luo and Yang Wu},
journal = {Hereditas},
year = {2026},
month = may,
doi = {10.1186/s41065-026-00692-9},
url = {https://doi.org/10.1186/s41065-026-00692-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Identification and validation of biomarkers associated with mitotic catastrophe in high-altitude hypoxia
AU - Wenwen Zhao
AU - Defang Liu
AU - Ting Luo
AU - Yang Wu
PY - 2026
DA - 2026/05/21
JO - Hereditas
DO - 10.1186/s41065-026-00692-9
UR - https://doi.org/10.1186/s41065-026-00692-9
AB - Background: High-altitude hypoxia (HAH) can cause adverse reactions, such as tinnitus and barotrauma, but the role of mitotic catastrophe (MC) in HAH remains unreported. This study investigated MC-associated biomarkers in HAH. Methods: HAH-related datasets and MC-related genes (MC-RGs) were retrieved from public databases. Differentially expressed genes (DEGs) between the HAH and control groups were screened, and overlapping genes between DEGs and MC-RGs were defined as candidates. Biomarkers were identified using three machine learning methods, receiver operating characteristic curve analysis, and expression validation. A nomogram was constructed for diagnostic assessment. Functional enrichment, immune infiltration, regulatory network, and drug prediction analyses were performed, with biomarker expression verified by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: DIAPH1 and MDM4 were confirmed as MC-associated biomarkers in HAH, and the nomogram displayed excellent diagnostic ability (area under the curve = 0.929). These biomarkers were coenriched in pathways such as oxidative phosphorylation. DIAPH1 was positively correlated with the infiltration of resting NK cells, whereas MDM4 was negatively correlated with that of M2 macrophages. A transcription factor–mRNA–miRNA network was established, with USF2 and GATA2 jointly targeting both biomarkers. Drugs such as rescinnamine targeted MDM4. RT-qPCR verified that USF2 and GATA2 were significantly downregulated in HAH (both P < 0.01), consistent with the bioinformatics results. Conclusions: DIAPH1 and MDM4 are valid MC-associated biomarkers for HAH. This study provides novel insights into HAH prevention and treatment. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s41065-026-00692-9.
SN - 0018-0661
SN - 1601-5223
ER -