Research progress of glioma-related molecular markers

Volume 5, Issue 2, April 2020     |     PP. 30-49      |     PDF (232 K)    |     Pub. Date: May 10, 2020
DOI:    245 Downloads     3704 Views  


Lai Xiong, Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, P.R. China
Xiao Qi Xie, Department of Critical Care Medicine, West China Hospital, Sichuan University, Sichuan, P.R. China
Wei Ming Li, Precision medicine center, West China Hospital, Sichuan University, Sichuan, P.R. China
Xin Wu, Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, P.R. China
Yong Luo, Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, P.R. China
Ping Ai, Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, P.R. China
Feng Wang, Department of Medical Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, P.R. China
Deng Bing Wu, Cancer Hospital, Ansteel Group Hospital, Anshan, Liao Ning, P.R. China
Yuan Zhao Liu, Department of Radiotherapy, Beijing Hospital, Beijing, P.R. China
Jing Bo Kang, Department of Radiotherapy, The Sixth Medical Center of PLA General Hospital, Beijing, P.R. China
RuoYuWang, Department of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian China
Bao Lin Qu, Department of Radiotherapy, Chinese PLA General Hospital, Beijing, P.R. China
Xian Feng Li, Department of Radiotherapy, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China
Jun Jie Wang, Department of Radiation Oncology Cancer Center Peking University 3rd Hospital P.R. China

Glioma is a primary brain tumor with a high incidence and a poor prognosis. Although it is treated by surgery, radiotherapy and other methods, the prognosis of patients is still not satisfactory. With the continuous development of medical technology, more and more Many biological molecular markers are recognized.The combined deletion of 1p / 19q is considered to be a characteristic molecular marker and independent prognostic factor in oligodendro glioma, and it can also be used as an important indicator to evaluate the sensitivity of chemotherapy. MGMT promoter methylated glioma patients are often more sensitive to chemotherapy drugs. IDH1 mutations occur widely in different types of gliomas such as oligodendroglioma and diffuse astrocytoma and suggest a good prognosis. The most common type of EGFR mutation is EGFRv III, which can enhance tumorigenicity, proliferation, migration and invasiveness of tumor cells. Positive EGFRv III in tumor tissues indicates a poor prognosis. CAR-targeting EGFRv III T-cell adoptive immunotherapy for glioblastoma multiforme has become a research hotspot. VEGF can promote angiogenesis in gliomas, and its expression is related to the pathological grade of gliomas. TERT activationMutations can enhance telomerase activity and lead to unlimited proliferation of tumor cells. The mutation rate of BRAF is higher in low-grade gliomas such as hairy cell astrocytoma and children's gliomas. ATRX gene mutation, TP53 gene mutation, ppENK activation Methylation of the daughter is also of diagnostic significance for the precise pathological typing of gliomas. In addition, some miRNAs and lnc RNAs have become a hot topic in the field of glioma molecular markers. With more and more of these molecules With the study of markers, we are continuously moving towards the precise diagnosis of glioma, individualized treatment and improvement of prognosis.

glioma, prognosis, molecular markers

Cite this paper
Lai Xiong, Xiao Qi Xie, Wei Ming Li, Xin Wu, Yong Luo, Ping Ai, Feng Wang, Deng Bing Wu, Yuan Zhao Liu, Jing Bo Kang, RuoYuWang, Bao Lin Qu, Xian Feng Li, Jun Jie Wang, Research progress of glioma-related molecular markers , SCIREA Journal of Clinical Medicine. Volume 5, Issue 2, April 2020 | PP. 30-49.


[ 1 ] Nikiforova M, Hamilton R. Molecular Diagnostics of Gliomas[J]. Archives of pathology & laboratory medicine, 2011, 135(5):558-568.
[ 2 ] Zhi-Liang, Wang, Chuan-Bao, et al. Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction.[J]. CNS neuroscience & therapeutics, 2019.
[ 3 ] Lassman A B , Iwamoto F M , Cloughesy T F , et al. International retrospective study of over 1000 adults with anaplastic oligodendroglial tumors[J]. Neuro-Oncology(6):6.
[ 4 ] Aldape K , Burger P C , Perry A . Clinicopathologic aspects of 1p/19q loss and the diagnosis of oligodendroglioma[J]. Archives of Pathology & Laboratory Medicine, 2007, 131(2):242-251.
[ 5 ] Zhao J, Ma W, Zhao H. Loss of heterozygosity 1p/19q and survival in glioma: a meta-analysis [J]. Neuro Oncol, 2014, 16(1): 103-112.
[ 6 ] Abrunhosa-Branquinho AN, Bar-Deroma R, Collette S, et al. Radiotherapy quality assurance for the RTOG 0834/EORTC 26053-22054/NCIC CTG CEC.1/CATNON intergroup trial "concurrent and adjuvant temozolomide chemotherapy in newly diagnosed non-1p/19q deleted anaplastic glioma": Individual case review analysis [J]. Radiother Oncol, 2018, 127(2): 292-298.
[ 7 ] Cairncross G, Wang M, Shaw E, et al.: Phase III Trial of Chemoradiotherapy for Anaplastic Oligodendroglioma: Long-Term Results of RTOG 9402. Journal of Clinical Oncology Official Journal of the American Society of Clinical Oncology 31: 337-343.
[ 8 ] Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Newly Diagnosed Anaplastic Oligodendroglioma: Long-Term Follow-Up of EORTC Brain Tumor Group Study 26951. Journal of Clinical Oncology 31: 344-350.
[ 9 ] Hashimoto N, Murakami M, Takahashi Y, Fujimoto M, Inazawa J and Mineura K: Correlation between genetic alteration and long-term clinical outcome of patients with oligodendroglial tumors, with identification of a consistent region of deletion on chromosome arm 1p. Cancer 97: 2254-2261.
[ 10 ] Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma[J]. N Engl J Med, 2005,352(10):997-1003.
[ 11 ] Mur P, Rodriguez de Lope A, Diaz-Crespo FJ, et al. Impact on prognosis of the regional distribution of MGMT methylation with respect to the CpG island methylator phenotype and age in glioma patients [J]. J Neurooncol, 2015, 122(3): 441-450.
[ 12 ] Okada M, Miyake K, Tamiya T. Glioblastoma Treatment in the Elderly[J]. Neurol Med Chir(Tokyo), 2017, 57(12):667-676.
[ 13 ] Weller M, Tabatabai G, Kästner B, et al. MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR trial [J]. Clinical Cancer Research, 2015, 21(9): 2057-2064.
[ 14 ] Zhao H, Wang S, Song C, Zha Y and Li L. The prognostic value of MGMT promoter status by pyrosequencing assay for glioblastoma patients’ survival: a meta-analysis. World Journal of Surgical Oncology 14: 261.
[ 15 ] Binabaj M, Bahrami A, Shahid Sales S, et al. The prognostic value of MGMT promoter methylation in glioblastoma: A meta-analysis of clinical trials[J]. J Cell Physiol, 2018, 233(1):378-386.
[ 16 ] Kim YR, Kim KH, Lee S, et al. Expression patterns of members of the isocitrate dehydrogenase gene family in murine inner ear [J]. Biotech Histochem, 2017, 92(7): 536-544.
[ 17 ] Bleeker F, Atai N , Lamba S , et al. The prognostic IDH1 R132mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma[J]. Acta Neuropathologica, 2010, 119(4):487-494.
[ 18 ] Deng L, Xiong P, Luo Y, et al. Association between IDH1/2 mutations and brain glioma grade [J]. Oncol Lett, 2018, 16(4): 5405-5409.
[ 19 ] Sonoda Y, Kumabe T, Nakamura T, et al. Analysis of IDH1 and IDH2 mutations in Japanese glioma patients [J]. Cancer Sci, 2009, 100(10): 1996-1998.
[ 20 ] Lee JJ, Murphy GF, Lian CG. Melanoma epigenetics: novel mechanisms, markers, and medicines [J]. Lab Invest, 2014, 94(8): 822-838.
[ 21 ] Panagopoulos I, Gorunova L, Taksdal I, et al. Recurrent 12q13-15 chromosomal aberrations, high frequency of isocitrate dehydrogenase 1 mutations, and absence of high mobility group AT-hook 2 expression in periosteal chondromas[J]. Oncology Letters, 2015.
[ 22 ] Saha S K, Parachoniak C A, Bardeesy N. IDH mutations in liver cell plasticity and biliary cancer[J]. Cell cycle (Georgetown, Tex.), 2014, 13(20):3176-3182.
[ 23 ] Boutzen, Héléna, Saland E, Larrue, Clément, et al. Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia[J]. The Journal of Experimental Medicine, 2016:jem.20150736.
[ 24 ] Marianne Labussière, Rahimian A, Giry M, et al. Chromosome 17p Homodisomy Is Associated With Better Outcome in 1p19q Non-Codeleted and IDH-Mutated Gliomas[J]. The Oncologist, 2016, 21(9):1131.
[ 25 ] Zhang H, Berezov A, Wang Q , et al. ErbB receptors: from oncogenes to targeted cancer therapies[J]. Journal of Clinical Investigation, 2007, 117(8):2051-8.
[ 26 ] Vecchio C A D, Jensen K C, Nitta R T, et al. Epidermal Growth Factor Receptor Variant III Contributes to Cancer Stem Cell Phenotypes in Invasive Breast Carcinoma[J].Cancer Research, 2012, 72(10):2657-2671.
[ 27 ] Hatanpaa K J, Burma S, Zhao D, et al. Epidermal Growth Factor Receptor in Glioma: Signal Transduction, Neuropathology, Imaging, and Radioresistance[J]. Neoplasia, 2010, 12(9):675-684.
[ 28 ] Chang S H, Chung Y S, Hwang S K, et al. Lentiviral vector-mediated shRNA against AIMP2-DX2 suppresses lung cancer cell growth through blocking glucose uptake[J]. Molecules and Cells, 2012, 33(6):553-562.
[ 29 ] Li G, Mitra S, Wong A J. The Epidermal Growth Factor Variant III Peptide Vaccine for Treatment of Malignant Gliomas[J]. NEUROSURGERY CLINICS OF NORTH AMERICA, 2010, 21(1):87-93.
[ 30 ] Gan H K, Kaye A H, Luwor R B. The EGFRvIII variant in glioblastoma multiforme[J]. Journal of Clinical Neuroscience, 2009, 16(6):0-754.
[ 31 ] Salkeni M A, Zarzour A, Tracy Y. Detection of EGFRvIII mutant DNA in the peripheral blood of brain tumor patients[J]. Journal of Neuro-Oncology, 2013, 115(1):27-35.
[ 32 ] Maher, John. Immunotherapy of Malignant Disease Using Chimeric Antigen Receptor Engrafted T Cells[J]. ISRN Oncology, 2012, 2012:1-23.
[ 33 ] Johnson L A, Scholler J, Ohkuri T, et al. Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma[J]. Science Translational Medicine, 2015, 7(275):275ra22-275ra22.
[ 34 ] Sampson J H, Archer G E, Mitchell D A, et al. Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant glioma[J]. Seminars in Immunology, 2008, 20(5):0-275.
[ 35 ] Lin Y, Zhai E, Liao B, et al. Autocrine VEGF signaling promotes cell proliferation through a PLC-dependent pathway and modulates Apatinib treatment efficacy in gastric cancer[J]. Oncotarget, 2017, 8(7).
[ 36 ] Yuan X, Liu D, Wang Y, et al. Significance of nuclear magnetic resonance combined with Ki-67 and VEGF detection in the diagnosis and prognosis evaluation of brain glioma [J]. J BUON, 2018, 23(2): 410-415.
[ 37 ] Huang D S, Wang Z, He X J , et al. Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation[J]. European Journal of Cancer, 2015, 51(8):969-976.
[ 38 ] Zhou P, Wei L, Xia X, et al. Association between telomerase reverse transcriptase rs2736100 polymorphism and risk of glioma[J]. Journal of Surgical Research, 2014, 191(1):156-160.
[ 39 ] Huy, Gia, Vuong, et al. TERT promoter mutation and its interaction with IDH mutations in glioma: Combined TERT promoter and IDH mutations stratifies lower-grade glioma into distinct survival subgroups—A meta-analysis of aggregate data[J]. Critical Reviews in Oncology/Hematology, 2017.
[ 40 ] Nonoguchi N, Ohta T, Oh J E, et al. TERT promoter mutations in primary and secondary glioblastomas[J]. Acta Neuropathologica, 2013, 126(6):931-937.
[ 41 ] Arita H, Narita Y, Fukushima S, et al. Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss[J]. Acta Neuropathologica, 2013, 126(2).
[ 42 ] Schindler G, Capper D, Meyer J, et al. Analysis ofBRAFV600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma[J]. Acta Neuropathologica, 2011, 121(3):397-405.
[ 43 ] Jones D T W, Kocialkowski S, Liu L, et al. Tandem Duplication Producing a Novel Oncogenic BRAF Fusion Gene Defines the Majority of Pilocytic Astrocytomas[J]. Cancer Research, 2008, 68(21):8673-8677.
[ 44 ] Tanaka S, Nakada M, Nobusawa S, et al. Epithelioid glioblastoma arising from pleomorphic xanthoastrocytoma with the BRAF V600E mutation[J]. Brain Tumor Pathology, 2014, 31(3):172-176.
[ 45 ] Keith T, Flaherty, Caroline, et al. Schadendorf.Improved survival with MEK inhibition in BRAF-mutated melanoma.[J].The New England journal of medicine,2012,367(2):107-14.
[ 46 ] Forschner A, Zips D, Schraml C, et al. Radiation recall dermatitis and radiation pneumonitis during treatment with vemurafenib[J]. Melanoma Research, 2014, 24(5):512-516.
[ 47 ] Suzuki H, Aoki K, Chiba K, et al. Mutational landscape and clonal architecture in grade II and III gliomas[J]. Nature Genetics, 2015, 47(5):458-468.
[ 48 ] Liu X Y, Gerges N, Korshunov A, et al. Frequent ATRX mutations and loss of expression in adult diffuse astrocytic tumors carryingIDH1/IDH2andTP53mutations[J]. Acta Neuropathologica, 2012, 124(5):615-625.
[ 49 ] Wiestler B, Capper D, Tim Holland-Letz. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup ofIDHmutant astrocytic tumors with better prognosis[J]. Acta Neuropathologica, 2013, 126(3):443-451.
[ 50 ] Ohgaki H, Kleihues P. Genetic Pathways to Primary and Secondary Glioblastoma[J]. American Journal of Pathology, 2007, 170(5):0-1453.
[ 51 ] Kim Y H, Nobusawa S, Mittelbronn M, et al. Molecular Classification of Low-Grade Diffuse Gliomas[J]. American Journal Of Pathology, 2010, 177(6):2708-2714.
[ 52 ] Kim Y H, Nobusawa S, Mittelbronn M, et al. Molecular Classification of Low-Grade Diffuse Gliomas[J]. American Journal Of Pathology, 2010, 177(6):2708-2714.
[ 53 ] Bleeker F E, Molenaar R J, Leenstra S. Recent advances in the molecular understanding of glioblastoma[J]. Journal of Neuro-Oncology, 2012, 108(1):11-27.
[ 54 ] Toraih E A, Aly N M, Abdallah H Y, et al. MicroRNA–target cross-talks: Key players in glioblastoma multiforme[J]. Tumor Biology, 2017, 39(11):101042831772684.
[ 55 ] Rolle K. miRNA Multiplayers in glioma. From bench to bedside[J]. Acta Biochimica Polonica, 2015, 62(3):353-365.
[ 56 ] Lai N S, Wu D G, Fang X G, et al. Serum microRNA-210 as a potential noninvasive biomarker for the diagnosis and prognosis of glioma[J]. British Journal of Cancer, 2015, 112(7):1241-1246.
[ 57 ] Qian Z, Li Y, Fan X, et al. Prognostic value of a microRNA signature as a novel biomarker in patients with lower-grade gliomas[J]. Journal of Neuro-Oncology, 2017.
[ 58 ] Zhang C, Li C, Li J, et al. Identification of miRNA-Mediated Core Gene Module for Glioma Patient Prediction by Integrating High-Throughput miRNA, mRNA Expression and Pathway Structure[J]. PLOS ONE, 2014, 9.
[ 59 ] Sujaya S, Pia P, Kumaravel S, et al. A Ten-microRNA Expression Signature Predicts Survival in Glioblastoma[J]. PLoS ONE, 2011, 6(3):e17438-.
[ 60 ] Xiao H, Bai J, Yan M, et al. Discovery of a novel two-miRNA signature predicting survival of Brain Lower Grade Glioma patients [J]. World Neurosurg, 2019.
[ 61 ] Lu Z , Tang H, Wu D, et al. Amplified voltammetric detection of miRNA from serum samples of glioma patients via combination of conducting magnetic microbeads and ferrocene-capped gold nanoparticle/streptavidin conjugates[J]. Biosensors and Bioelectronics, 2016, 86:502-507.
[ 62 ] Yoon J H, Abdelmohsen K, Gorospe M. Posttranscriptional Gene Regulation by Long Noncoding RNA[J]. Journal of Molecular Biology, 2013, 425(19):3723-3730.
[ 63 ] Zhou X, Ren Y, Zhang J, et al. HOTAIR is a therapeutic target in glioblastoma[J]. Oncotarget, 2015, 6(10).
[ 64 ] Jun-Xia Z, Lei H, Zhao-Shi B, et al. HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma[J]. Neuro-Oncology(12):12.
[ 65 ] Zhang X, Sun S, Pu J, et al. Long non-coding RNA expression profiles predict clinical phenotypes in glioma[J]. Neurobiology of Disease, 2012, 48(1):1-8.
[ 66 ] Zhang X Q, Sun S, Lam K F, et al. A long non-coding RNA signature in glioblastoma multiforme predicts survival[J]. Neurobiology of Disease, 2013, 58:123-131.