Academic Journal
Cellular hierarchy framework based on single-cell/multi-patient sample sequencing reveals metabolic biomarker PYGL as a therapeutic target for HNSCC
| العنوان: | Cellular hierarchy framework based on single-cell/multi-patient sample sequencing reveals metabolic biomarker PYGL as a therapeutic target for HNSCC |
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| المؤلفون: | Guan, Jiezhong, Xu, Xi, Qiu, Guo, He, Chong, Lu, Xiaoyue, Wang, Kang, Liu, Xinyu, Li, Yuanyuan, Ling, Zihang, Tang, Xuan, Liang, Yujie, Tao, Xiaoan, Cheng, Bin, Yang, Bo |
| المساهمون: | National Natural Science Foundation of China, Basic and Applied Basic Research Foundation of Guangdong Province, Scientific and Technological Planning Project of Guangzhou City, State Key Laboratory of Oral Disease, Open Funding of Guangdong Provincial Key Laboratory of Stomatology, Special Funds for the Cultivation of Guangdong College Students' Scientific and Technological Innovation, Undergraduate Training Program for Innovation and Entrepreneurship of Sun Yat-sen University |
| المصدر: | Journal of Experimental & Clinical Cancer Research ; volume 42, issue 1 ; ISSN 1756-9966 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2023 |
| الوصف: | Background A growing body of research has revealed the connection of metabolism reprogramming and tumor progression, yet how metabolism reprogramming affects inter-patient heterogeneity and prognosis in head and neck squamous cell carcinoma (HNSCC) still requires further explorations. Methods A cellular hierarchy framework based on metabolic properties discrepancy, METArisk, was introduced to re-analyze the cellular composition from bulk transcriptomes of 486 patients through deconvolution utilizing single-cell reference profiles from 25 primary and 8 metastatic HNSCC sample integration of previous studies. Machine learning methods were used to identify the correlations between metabolism-related biomarkers and prognosis. The functions of the genes screened out in tumor progression, metastasis and chemotherapy resistance were validated in vitro by cellular functional experiments and in vivo by xenograft tumor mouse model. Results Incorporating the cellular hierarchy composition and clinical properties, the METArisk phenotype divided multi-patient cohort into two classes, wherein poor prognosis of METArisk-high subgroup was associated with a particular cluster of malignant cells with significant activity of metabolism reprogramming enriched in metastatic single-cell samples. Subsequent analysis targeted for phenotype differences between the METArisk subgroups identified PYGL as a key metabolism-related biomarker that enhances malignancy and chemotherapy resistance by GSH/ROS/p53 pathway, leading to poor prognosis of HNSCC. Conclusion PYGL was identified as a metabolism-related oncogenic biomarker that promotes HNSCC progression, metastasis and chemotherapy resistance though GSH/ROS/p53 pathway. Our study revealed the cellular hierarchy composition of HNSCC from the cell metabolism reprogramming perspective and may provide new inspirations and therapeutic targets for HNSCC in the future. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s13046-023-02734-w |
| DOI: | 10.1186/s13046-023-02734-w.pdf |
| DOI: | 10.1186/s13046-023-02734-w/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s13046-023-02734-w https://link.springer.com/content/pdf/10.1186/s13046-023-02734-w.pdf https://link.springer.com/article/10.1186/s13046-023-02734-w/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.19D6D95D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13046-023-02734-w |
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