We appreciate the generosity of CGGA and TCGA network for sharing the huge amount of data.
Author contributions
FY conceived the project. CM and FY supervised the project. FY, YW and XC downloaded the data and performed the statistical analysis. CM, FY, YW, XC, CD, JZ, CT and JY interpreted the results. All listed authors read and approved the final manuscript.
Conflicts of interest
The authors declare no conflicts of interest in this manuscript.
Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS.CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015. Neuro Oncol. 2018;20:iv1–86. Erratum in: Neuro Oncol. 2018;23:508–22. [DOI] [PubMed] [PMC]
Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021;23:1231–51. [DOI] [PubMed] [PMC]
van den Bent MJ.Chemotherapy for low-grade glioma: when, for whom, which regimen?Curr Opin Neurol. 2015;28:633–938. [DOI] [PubMed]
Schiff D, Van den Bent M, Vogelbaum MA, Wick W, Miller CR, Taphoorn M, et al. Recent developments and future directions in adult lower-grade gliomas: society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) consensus. Neuro Oncol. 2019;21:837–53. [DOI] [PubMed] [PMC]
van den Bent MJ.Interobserver variation of the histopathological diagnosis in clinical trials on glioma: a clinician’s perspective. Acta Neuropathol. 2010;120:297–304. [DOI] [PubMed] [PMC]
Wen PY, Packer RJ.The 2021 WHO classification of tumors of the central nervous system: clinical implications. Neuro Oncol. 2021;23:1215–7. [DOI] [PubMed] [PMC]
Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360:765–73. [DOI] [PubMed] [PMC]
Cairncross JG, Wang M, Jenkins RB, Shaw EG, Giannini C, Brachman DG, et al. Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH. J Clin Oncol. 2014;32:783–90. [DOI] [PubMed] [PMC]
Speirs CK, Simpson JR, Robinson CG, DeWees TA, Tran DD, Linette G, et al. Impact of 1p/19q codeletion and histology on outcomes of anaplastic gliomas treated with radiation therapy and temozolomide. Int J Radiat Oncol Biol Phys. 2015;91:268–76. [DOI] [PubMed]
Arita H, Matsushita Y, Machida R, Yamasaki K, Hata N, Ohno M, et al. TERT promoter mutation confers favorable prognosis regardless of 1p/19q status in adult diffuse gliomas with IDH1/2 mutations. Acta Neuropathol Commun. 2020;8:201. [DOI] [PubMed] [PMC]
Spino M, Snuderl M.Genomic molecular classification of CNS malignancies. Adv Anat Pathol. 2020;27:44–50. [DOI] [PubMed]
Pan T.N6-methyl-adenosine modification in messenger and long non-coding RNA. Trends Biochem Sci. 2013;38:204–9. [DOI] [PubMed] [PMC]
Ma S, Chen C, Ji X, Liu J, Zhou Q, Wang G, et al. The interplay between m6A RNA methylation and noncoding RNA in cancer. J Hematol Oncol. 2019;12:121. [DOI] [PubMed] [PMC]
Wang Y, Gao M, Zhu F, Li X, Yang Y, Yan Q, et al. METTL3 is essential for postnatal development of brown adipose tissue and energy expenditure in mice. Nat Commun. 2020;11:1648. [DOI] [PubMed] [PMC]
Fustin JM, Doi M, Yamaguchi Y, Hida H, Nishimura S, Yoshida M, et al. RNA-methylation-dependent RNA processing controls the speed of the circadian clock. Cell. 2013;155:793–806. [DOI] [PubMed]
Engel M, Eggert C, Kaplick PM, Eder M, Röh S, Tietze L, et al. The role of m6A/m-RNA methylation in stress response regulation. Neuron. 2018;99:389–403.e9. [DOI] [PubMed] [PMC]
Chen XY, Zhang J, Zhu JS.The role of m6A RNA methylation in human cancer. Mol Cancer. 2019;18:103. [DOI] [PubMed] [PMC]
Edens BM, Vissers C, Su J, Arumugam S, Xu Z, Shi H, et al. FMRP modulates neural differentiation through m6A-dependent mRNA nuclear export. Cell Rep. 2019;28:845–54.e5. [DOI] [PubMed] [PMC]
Yu R, Li Q, Feng Z, Cai L, Xu Q.m6A reader YTHDF2 regulates LPS-induced inflammatory response. Int J Mol Sci. 2019;20:1323. [DOI] [PubMed] [PMC]
Shen C, Xuan B, Yan T, Ma Y, Xu P, Tian X, et al. m6A-dependent glycolysis enhances colorectal cancer progression. Mol Cancer. 2020;19:72. [DOI] [PubMed] [PMC]
Leung AKL.The whereabouts of microRNA actions: cytoplasm and beyond. Trends Cell Biol. 2015;25:601–10. [DOI] [PubMed] [PMC]
Peng Y, Croce CM.The role of microRNAs in human cancer. Signal Transduct Target Ther. 2016;1:15004. [DOI] [PubMed] [PMC]
Qu S, Guan J, Liu Y.Identification of microRNAs as novel biomarkers for glioma detection: a meta-analysis based on 11 articles. J Neurol Sci. 2015;348:181–7. [DOI] [PubMed]
Banelli B, Forlani A, Allemanni G, Morabito A, Pistillo MP, Romani M.MicroRNA in glioblastoma: an overview. Int J Genomics. 2017;2017:7639084. [DOI] [PubMed] [PMC]
Ma C, Nguyen HPT, Luwor RB, Stylli SS, Gogos A, Paradiso L, et al. A comprehensive meta-analysis of circulation miRNAs in glioma as potential diagnostic biomarker. PLoS One. 2018;13:e0189452. [DOI] [PubMed] [PMC]
Chong W, Shang L, Liu J, Fang Z, Du F, Wu H, et al. m6A regulator-based methylation modification patterns characterized by distinct tumor microenvironment immune profiles in colon cancer. Theranostics. 2021;11:2201–17. [DOI] [PubMed] [PMC]
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102:15545–50. [DOI] [PubMed] [PMC]
Ostrom QT, Cote DJ, Ascha M, Kruchko C, Barnholtz-Sloan JS.Adult glioma incidence and survival by race or ethnicity in the United States from 2000 to 2014. JAMA Oncol. 2018;4:1254–62. [DOI] [PubMed] [PMC]
Ebert MS, Sharp PA.Roles for microRNAs in conferring robustness to biological processes. Cell. 2012;149:515–24. [DOI] [PubMed] [PMC]
Kasinski AL, Slack FJ.Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011;11:849–64. [DOI] [PubMed] [PMC]
Stahlhut C, Slack FJ.MicroRNAs and the cancer phenotype: profiling, signatures and clinical implications. Genome Med. 2013;5:111. [DOI] [PubMed] [PMC]
Otmani K, Lewalle P.Tumor suppressor miRNA in cancer cells and the tumor microenvironment: mechanism of deregulation and clinical implications. Front Oncol. 2021;11:708765. [DOI] [PubMed] [PMC]
He K, Li WX, Guan D, Gong M, Ye S, Fang Z, et al. Regulatory network reconstruction of five essential microRNAs for survival analysis in breast cancer by integrating miRNA and mRNA expression datasets. Funct Integr Genomics. 2019;19:645–58. [DOI] [PubMed]
Lizarte Neto FS, Rodrigues AR, Trevisan FA, de Assis Cirino ML, Matias CCMS, Pereira-da-Silva G, et al. microRNA-181d associated with the methylation status of the MGMT gene in Glioblastoma multiforme cancer stem cells submitted to treatments with ionizing radiation and temozolomide. Brain Res. 2019;1720:146302. [DOI] [PubMed]
Pyman B, Sedghi A, Azizi S, Tyryshkin K, Renwick N, Mousavi P.Exploring microRNA regulation of cancer with context-aware deep cancer classifier. Pac Symp Biocomput. 2019;24:160–71. [DOI] [PubMed]
Tabibkhooei A, Izadpanahi M, Arab A, Zare-Mirzaei A, Minaeian S, Rostami A, et al. Profiling of novel circulating microRNAs as a non-invasive biomarker in diagnosis and follow-up of high and low-grade gliomas. Clin Neurol Neurosurg. 2020;190:105652. [DOI] [PubMed]
Alarcón CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF.N6-methyladenosine marks primary microRNAs for processing. Nature. 2015;519:482–5. [DOI] [PubMed] [PMC]
Cho YK, Son Y, Kim SN, Song HD, Kim M, Park JH, et al. MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling. Mol Metab. 2019;29:86–98. [DOI] [PubMed] [PMC]
Rahmanian S, Murad R, Breschi A, Zeng W, Mackiewicz M, Williams B, et al. Dynamics of microRNA expression during mouse prenatal development. Genome Res. 2019;29:1900–9. [DOI] [PubMed] [PMC]
Wu CJ, Cho S, Huang HY, Lu CH, Russ J, Cruz LO, et al. MiR-23~27~24-mediated control of humoral immunity reveals a TOX-driven regulatory circuit in follicular helper T cell differentiation. Sci Adv. 2019;5:eaaw1715. [DOI] [PubMed] [PMC]
Cen B, Lang JD, Du Y, Wei J, Xiong Y, Bradley N, et al. Prostaglandin E2 induces miR675-5p to promote colorectal tumor metastasis via modulation of p53 expression. Gastroenterology. 2020;158:971–84.e10. [DOI] [PubMed] [PMC]
Zhang J, Bai R, Li M, Ye H, Wu C, Wang C, et al. Excessive miR-25-3p maturation via N6-methyladenosine stimulated by cigarette smoke promotes pancreatic cancer progression. Nat Commun. 2019;10:1858. [DOI] [PubMed] [PMC]
Han J, Wang JZ, Yang X, Yu H, Zhou R, Lu HC, et al. METTL3 promote tumor proliferation of bladder cancer by accelerating pri-miR221/222 maturation in m6A-dependent manner. Mol Cancer. 2019;18:110. [DOI] [PubMed] [PMC]
Gu S, Sun D, Dai H, Zhang Z.N6-methyladenosine mediates the cellular proliferation and apoptosis via microRNAs in arsenite-transformed cells. Toxicol Lett. 2018;292:1–11. [DOI] [PubMed]
Ma JZ, Yang F, Zhou CC, Liu F, Yuan JH, Wang F, et al. METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N6-methyladenosine-dependent primary microRNA processing. Hepatology. 2017;65:529–43. [DOI] [PubMed]
Chang YZ, Chai RC, Pang B, Chang X, An SY, Zhang KN, et al. METTL3 enhances the stability of MALAT1 with the assistance of HuR via m6A modification and activates NF-κB to promote the malignant progression of IDH-wildtype glioma. Cancer Lett. 2021;511:36–46. [DOI] [PubMed]
Chai RC, Chang YZ, Chang X, Pang B, An SY, Zhang KN, et al. YTHDF2 facilitates UBXN1 mRNA decay by recognizing METTL3-mediated m6A modification to activate NF-κB and promote the malignant progression of glioma. J Hematol Oncol. 2021;14:109. [DOI] [PubMed] [PMC]
Dong F, Qin X, Wang B, Li Q, Hu J, Cheng X, et al. ALKBH5 facilitates hypoxia-induced paraspeckle assembly and IL8 secretion to generate an immunosuppressive tumor microenvironment. Cancer Res. 2021;81:5876–88. [DOI] [PubMed]
Li Y, Xu J, Zhang J, Zhang J, Zhang J, Lu X.MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB. Cancer Cell Int. 2019;19:294. [DOI] [PubMed] [PMC]
Gabriely G, Yi M, Narayan RS, Niers JM, Wurdinger T, Imitola J, et al. Human glioma growth is controlled by microRNA-10b. Cancer Res. 2011;71:3563–72. [DOI] [PubMed] [PMC]
Chen W, Zhang B, Guo W, Gao L, Shi L, Li H, et al. miR-429 inhibits glioma invasion through BMK1 suppression. J Neurooncol. 2015;125:43–54. [DOI] [PubMed]
Santangelo A, Imbrucè P, Gardenghi B, Belli L, Agushi R, Tamanini A, et al. A microRNA signature from serum exosomes of patients with glioma as complementary diagnostic biomarker. J Neurooncol. 2018;136:51–62. [DOI] [PubMed]
Baraniskin A, Kuhnhenn J, Schlegel U, Maghnouj A, Zöllner H, Schmiegel W, et al. Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma. Neuro Oncol. 2012;14:29–33. [DOI] [PubMed] [PMC]
Jiang P, Gu S, Pan D, Fu J, Sahu A, Hu X, et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat Med. 2018;24:1550–8. [DOI] [PubMed] [PMC]
Cancer Genome Atlas Research Network; Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med. 2015;372:2481–98. [DOI] [PubMed] [PMC]