Expression and Prognostic Role of PANK1 in Glioma


Citar

Texto integral

Resumo

Background:Malignant gliomas are the most common type of primary malignant brain tumors. Pantothenate kinase 1 (PANK1) mRNA is highly expressed in several metabolic processes, implying that PANK1 plays a potential role in metabolic programming in cancers. However, the role of PANK1 in glioma has not been fully explored.

Methods:Public datasets (The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gravendeel and Rembrandt) and validation cohort were used to explore the expression of PANK1 in glioma tissues. Kaplan–Meier and Cox regression analyses were used to explore the relationship between PANK1 and prognosis in glioma. Cell proliferation and invasion were determined using Cell Counting Kit-8 (CCK8) and transwell invasion in vitro assays.

Results:Analysis using the four public datasets and the validation cohort showed that PANK1 expression was significantly downregulated in glioma tissues compared with non-tumor tissues (P(<0.01). PANK1 expression was negatively correlated with World Health Organization (WHO) grade, 1p/19q non-codeletion and isocitric dehydrogenase 1/2 (IDH1/2) wildtype. Furthermore, high expression of PANK1 was correlated with significantly better prognosis of glioma patients compared to patients with low expression of PANK1 (all P(<0.01 in the four datasets). Besides, both lower-grade glioma (LGG) and glioblastoma multiform (GBM) patients with high expression of PANK1 had a significantly better prognosis than those with low expression of PANK1 in TCGA, Gravendeel and Rembrandt datasets (all P (<0.01). Multivariate Cox regression analysis revealed that low PANK1 expression was an independent risk factor associated with a worse prognosis of glioma patients. Moreover, overexpression of PANK1 significantly inhibited the proliferation and invasion of U87 and U251 cells.

Conclusion:PANK1 expression is downregulated in glioma tissues and is a novel prognostic biomarker in glioma patients

Sobre autores

Zhiming Zhao

Department of Geriatrics, Renmin Hospital of Wuhan University

Autor responsável pela correspondência
Email: info@benthamscience.net

Xu Xu

Department of Geriatrics, Renmin Hospital of Wuhan University

Email: info@benthamscience.net

Shijing Ma

Department of Geriatrics, Renmin Hospital of Wuhan University

Email: info@benthamscience.net

Li Li

Department of Geriatrics, Renmin Hospital of Wuhan University

Email: info@benthamscience.net

Bibliografia

  1. Ostrom, Q.T.; Patil, N.; Cioffi, G.; Waite, K.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2013–2017. Neuro-oncol., 2020, 22(12), 1-96. doi: 10.1093/neuonc/noaa200 PMID: 33123732
  2. Brown, T.J.; Brennan, M.C.; Li, M.; Church, E.W.; Brandmeir, N.J.; Rakszawski, K.L.; Patel, A.S.; Rizk, E.B.; Suki, D.; Sawaya, R.; Glantz, M. Association of the extent of resection with survival in glioblastoma. JAMA Oncol., 2016, 2(11), 1460-1469. doi: 10.1001/jamaoncol.2016.1373 PMID: 27310651
  3. Eckel-Passow, J.E.; Lachance, D.H.; Molinaro, A.M.; Walsh, K.M.; Decker, P.A.; Sicotte, H.; Pekmezci, M.; Rice, T.; Kosel, M.L.; Smirnov, I.V.; Sarkar, G.; Caron, A.A.; Kollmeyer, T.M.; Praska, C.E.; Chada, A.R.; Halder, C.; Hansen, H.M.; McCoy, L.S.; Bracci, P.M.; Marshall, R.; Zheng, S.; Reis, G.F.; Pico, A.R.; O’Neill, B.P.; Buckner, J.C.; Giannini, C.; Huse, J.T.; Perry, A.; Tihan, T.; Berger, M.S.; Chang, S.M.; Prados, M.D.; Wiemels, J.; Wiencke, J.K.; Wrensch, M.R.; Jenkins, R.B. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N. Engl. J. Med., 2015, 372(26), 2499-2508. doi: 10.1056/NEJMoa1407279 PMID: 26061753
  4. Molinari, E.; Curran, O.E.; Grant, R. Clinical importance of molecular markers of adult diffuse glioma. Pract. Neurol., 2019, 19(5), 412-416. doi: 10.1136/practneurol-2018-002116 PMID: 31175262
  5. Leonardi, R.; Rehg, J.E.; Rock, C.O.; Jackowski, S. Pantothenate kinase 1 is required to support the metabolic transition from the fed to the fasted state. PLoS One, 2010, 5(6), e11107. doi: 10.1371/journal.pone.0011107 PMID: 20559429
  6. Leonardi, R.; Rock, C.O.; Jackowski, S. Pank1 deletion in leptin-deficient mice reduces hyperglycaemia and hyperinsulinaemia and modifies global metabolism without affecting insulin resistance. Diabetologia, 2014, 57(7), 1466-1475. doi: 10.1007/s00125-014-3245-5 PMID: 24781151
  7. Caniglia, J.L.; Jalasutram, A.; Asuthkar, S.; Sahagun, J.; Park, S.; Ravindra, A.; Tsung, A.J.; Guda, M.R.; Velpula, K.K. Beyond glucose: Alternative sources of energy in glioblastoma. Theranostics, 2021, 11(5), 2048-2057. doi: 10.7150/thno.53506 PMID: 33500708
  8. Yang, L.; Zhang, B.; Wang, X.; Liu, Z.; Li, J.; Zhang, S.; Gu, X.; Jia, M.; Guo, H.; Feng, N.; Fan, R.; Xie, M.; Pei, J.; Chen, L. P53/PANK1/miR‐107 signalling pathway spans the gap between metabolic reprogramming and insulin resistance induced by high‐fat diet. J. Cell. Mol. Med., 2020, 24(6), 3611-3624. doi: 10.1111/jcmm.15053 PMID: 32048816
  9. Wang, S.J.; Yu, G.; Jiang, L.; Li, T.; Lin, Q.; Tang, Y.; Gu, W. p53-dependent regulation of metabolic function through transcriptional activation of pantothenate kinase-1 gene. Cell Cycle, 2013, 12(5), 753-761. doi: 10.4161/cc.23597 PMID: 23343762
  10. Liu, Y.; Cheng, Z.; Li, Q.; Pang, Y.; Cui, L.; Qian, T.; Quan, L.; Dai, Y.; Jiao, Y.; Zhang, Z.; Ye, X.; Shi, J.; Fu, L. Prognostic significance of the PANK family expression in acute myeloid leukemia. Ann. Transl. Med., 2019, 7(12), 261. doi: 10.21037/atm.2019.05.28 PMID: 31355228
  11. Bowman, R.L.; Wang, Q.; Carro, A.; Verhaak, R.G.W.; Squatrito, M. GlioVis data portal for visualization and analysis of brain tumor expression datasets. Neuro-oncol., 2017, 19(1), 139-141. doi: 10.1093/neuonc/now247 PMID: 28031383
  12. Zhao, Z.; Zhang, K.N.; Wang, Q.; Li, G.; Zeng, F.; Zhang, Y.; Wu, F.; Chai, R.; Wang, Z.; Zhang, C.; Zhang, W.; Bao, Z.; Jiang, T. Chinese glioma genome atlas (CGGA): A comprehensive resource with functional genomic data from chinese glioma patients. Genomics Proteomics Bioinformatics, 2021, 19(1), 1-12. doi: 10.1016/j.gpb.2020.10.005 PMID: 33662628
  13. Rhodes, D.R.; Yu, J.; Shanker, K.; Deshpande, N.; Varambally, R.; Ghosh, D.; Barrette, T.; Pander, A.; Chinnaiyan, A.M. ONCOMINE: A cancer microarray database and integrated data-mining platform. Neoplasia, 2004, 6(1), 1-6. doi: 10.1016/S1476-5586(04)80047-2 PMID: 15068665
  14. Cerami, E.; Gao, J.; Dogrusoz, U.; Gross, B.E.; Sumer, S.O.; Aksoy, B.A.; Jacobsen, A.; Byrne, C.J.; Heuer, M.L.; Larsson, E.; Antipin, Y.; Reva, B.; Goldberg, A.P.; Sander, C.; Schultz, N. The cBio cancer genomics portal: An open platform for exploring multidimensional cancer genomics data. Cancer Discov., 2012, 2(5), 401-404. doi: 10.1158/2159-8290.CD-12-0095 PMID: 22588877
  15. Valk, P.J.M.; Verhaak, R.G.W.; Beijen, M.A.; Erpelinck, C.A.J.; van Doorn-Khosrovani, S.B.W.; Boer, J.M.; Beverloo, H.B.; Moorhouse, M.J.; van der Spek, P.J.; Löwenberg, B.; Delwel, R. Prognostically useful gene-expression profiles in acute myeloid leukemia. N. Engl. J. Med., 2004, 350(16), 1617-1628. doi: 10.1056/NEJMoa040465 PMID: 15084694
  16. Michelakis, E.D.; Sutendra, G.; Dromparis, P.; Webster, L.; Haromy, A.; Niven, E.; Maguire, C.; Gammer, T.L.; Mackey, J.R.; Fulton, D.; Abdulkarim, B.; McMurtry, M.S.; Petruk, K.C. Metabolic modulation of glioblastoma with dichloroacetate. Sci. Transl. Med., 2010, 2(31), 31ra34. doi: 10.1126/scitranslmed.3000677 PMID: 20463368
  17. Garcia, J.H.; Jain, S.; Aghi, M.K. Metabolic drivers of invasion in glioblastoma. Front. Cell Dev. Biol., 2021, 9, 683276. doi: 10.3389/fcell.2021.683276 PMID: 34277624
  18. Kesarwani, P.; Prabhu, A.; Kant, S.; Chinnaiyan, P. Metabolic remodeling contributes towards an immune-suppressive phenotype in glioblastoma. Cancer Immunol. Immunother., 2019, 68(7), 1107-1120. doi: 10.1007/s00262-019-02347-3 PMID: 31119318
  19. Rock, C.O.; Calder, R.B.; Karim, M.A.; Jackowski, S. Pantothenate kinase regulation of the intracellular concentration of coenzyme A. J. Biol. Chem., 2000, 275(2), 1377-1383. doi: 10.1074/jbc.275.2.1377 PMID: 10625688
  20. Touat, M.; Idbaih, A.; Sanson, M.; Ligon, K.L. Glioblastoma targeted therapy: Updated approaches from recent biological insights. Ann. Oncol., 2017, 28(7), 1457-1472. doi: 10.1093/annonc/mdx106 PMID: 28863449
  21. Pathmanapan, S.; Ilkayeva, O.; Martin, J.T.; Loe, A.K.H.; Zhang, H.; Zhang, G.F.; Newgard, C.B.; Wunder, J.S.; Alman, B.A. Mutant IDH and non-mutant chondrosarcomas display distinct cellular metabolomes. Cancer Metab., 2021, 9(1), 13. doi: 10.1186/s40170-021-00247-8 PMID: 33762012
  22. Cuddapah, V.A.; Robel, S.; Watkins, S.; Sontheimer, H. A neurocentric perspective on glioma invasion. Nat. Rev. Neurosci., 2014, 15(7), 455-465. doi: 10.1038/nrn3765 PMID: 24946761

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar

Declaração de direitos autorais © Bentham Science Publishers, 2024