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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Lu, Zhongwen Pan, Yongsheng Wang, Songbo Wu, Jiajin Miao, Chenkui Wang, Zengjun |
| Abstract | Glycolysis-related metabolic reprogramming is a central hallmark of human cancers, especially in renal cell carcinoma. However, the regulatory function of glycolytic signature in papillary RCC has not been well elucidated. In the present study, the glycolysis-immune predictive signature was constructed and validated using WGCNA, glycolysis-immune clustering analysis. PPI network of DEGs was constructed and visualized. Functional enrichments and patients’ overall survival were analyzed. QRT-PCR experiments were performed to detect hub genes’ expression and distribution, siRNA technology was used to silence targeted genes; cell proliferation and migration assays were applied to evaluate the biological function. Glucose concentration, lactate secretion, and ATP production were measured. Glycolysis-Immune Related Prognostic Index (GIRPI) was constructed and combined analyzed with single-cell RNA-seq. High-GIRPI signature predicted significantly poorer outcomes and relevant clinical features of pRCC patients. Moreover, GIRPI also participated in several pathways, which affected tumor immune microenvironment and provided potential therapeutic strategy. As a key glycolysis regulator, PFKFB3 could promote renal cancer cell proliferation and migration in vitro. Blocking of PFKFB3 by selective inhibitor PFK-015 or glycolytic inhibitor 2-DG significantly restrained renal cancer cells’ neoplastic potential. PFK-015 and sunitinib could synergistically inhibit pRCC cells proliferation. Glycolysis-Immune Risk Signature is closely associated with pRCC prognosis, progression, immune infiltration, and therapeutic response. PFKFB3 may serve as a pivotal glycolysis regulator and mediates Sunitinib resistance in pRCC patients. |
| Related Links | https://eurjmedres.biomedcentral.com/counter/pdf/10.1186/s40001-024-01808-5.pdf |
| Ending Page | 20 |
| Page Count | 20 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s40001-024-01808-5 |
| Journal | European Journal of Medical Research |
| Issue Number | 1 |
| Volume Number | 29 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-04-15 |
| Access Restriction | Open |
| Subject Keyword | Medicine Public Health Infectious Diseases Internal Medicine Surgery Oncology Biomedicine Papillary renal cell carcinoma Glycolysis-Immune Risk Signature Single-cell RNA-seq Immune infiltration Progression Sunitinib resistance Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
| Journal Impact Factor | 2.8/2023 |
| 5-Year Journal Impact Factor | 2.9/2023 |
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