دورية أكاديمية
Hypoxia within tumor microenvironment characterizes distinct genomic patterns and aids molecular subtyping for guiding individualized immunotherapy
| العنوان: | Hypoxia within tumor microenvironment characterizes distinct genomic patterns and aids molecular subtyping for guiding individualized immunotherapy |
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| المؤلفون: | Run Shi, Jing Sun, Hanyu Zhou, Tong Hu, Zhaojia Gao, Xin Wang, Minglun Li, Zhaokai Zhou, Yongqian Shu |
| المصدر: | Journal of Big Data, Vol 11, Iss 1, Pp 1-21 (2024) |
| بيانات النشر: | SpringerOpen, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Computer engineering. Computer hardware LCC:Information technology LCC:Electronic computers. Computer science |
| مصطلحات موضوعية: | Hypoxia, Tumor microenvironment, Molecular subtyping, Multi-omics, Precision medicine, Immunotherapy, Computer engineering. Computer hardware, TK7885-7895, Information technology, T58.5-58.64, Electronic computers. Computer science, QA75.5-76.95 |
| الوصف: | Abstract Assessing the hypoxic status within the tumor microenvironment (TME) is crucial for its significant clinical relevance in evaluating drug resistance and tailoring individualized strategies. In this study, we proposed a robust pan-cancer hypoxic quantification method utilizing multiple public databases, diverse bioinformatics, and statistical methods. All tumor samples were classified into four subtypes: non-hypoxic/TMEhigh (C1), hypoxic/TMEhigh (C2), non-hypoxic/TMElow (C3), and hypoxic/TMElow (C4). We systematically analyzed multi-omics data and single-cell RNA-sequencing (scRNA-seq) data to reveal distinct immune landscape patterns and genomic characteristics among the four subtypes across pan-cancer. Furthermore, we employed multiple machine learning approaches to construct a hypoxic-TME model to enhance the predictive accuracy of immunotherapy response. Additionally, drug repositioning was implemented for cancer patients predicted as non-responders to immunotherapy. A pan-cancer analysis identified PDK1 as a hub gene linking tumor hypoxia, glycolysis, and immunotherapy resistance. In vivo experimental validation further confirmed that targeting PDK1 could improve the response to immunotherapy. Overall, our study may offer valuable insights for integrating hypoxic-TME classification into tumor staging and providing personalized strategies for cancer patients. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2196-1115 |
| Relation: | https://doaj.org/toc/2196-1115 |
| DOI: | 10.1186/s40537-024-00945-2 |
| URL الوصول: | https://doaj.org/article/690fd745a68745e3a0cb4e7409f1ff13 |
| رقم الأكسشن: | edsdoj.690fd745a68745e3a0cb4e7409f1ff13 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 21961115 |
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| DOI: | 10.1186/s40537-024-00945-2 |