title: Genome-wide transcriptional analyses of Chinese patients reveal cell migration is attenuated in IDH1-mutant glioblastomas.
abstract: Patients with isocitrate dehydrogenase 1 (IDH1)-mutant glioblastoma exhibit increased survival compared with those with wild-type IDH1 tumors. The magnitude of this finding has led to the use of IDH1 mutations as diagnostic and prognostic biomarkers. However, the mechanisms underlying the reported correlation between the IDH1 mutation and increased survival have not been fully revealed. In this work, based on genome-wide transcriptional analyses of 69 Chinese patients with glioblastoma, we have found that the focal adhesion pathway is significantly downregulated in IDH1-mutant glioblastomas. The impaired focal adhesion leads to compromised cell migration and tumor invasion, contributing to the optimistic prognosis of these patients. Moreover, the signature genes of HIF-1α, the downstream factor of mutated IDH1, are found to be suppressed in IDH1-mutant gliomas. Given the role of HIF-1α in cell migration, we conclude that the attenuation of HIF-1α-dependent glioblastoma cell infiltration contributes to the better outcomes of patients with IDH1-mutant gliomas.
authors.affiliation: Beijing Neurosurgical Institute, No. 6 Tiantan Xili, Dongcheng District, 100050, Beijing, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, 100050, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Beijing Neurosurgical Institute, No. 6 Tiantan Xili, Dongcheng District, 100050, Beijing, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, 100050, Beijing, China.
authors.forename: Chuanbao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, 100050, Beijing, China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, 100050, Beijing, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: First Affiliated Hospital, Dalian Medical University, No. 9 Lvshun South Road, 116044, Dalian, Liaoning province, China.
authors.forename: Kuanyu
authors.initials: K
authors.lastname: Wang
authors.affiliation: Harbin Medical University, No. 157 Bao Jian Road, Nan Gang District, 150086, Harbin, Heilongjiang province, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Cai
authors.affiliation: China Medical University, No. 77 Pu He Road, Shen Bei New District, 110013, Shenyang, Liaoning province, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Beijing Neurosurgical Institute, No. 6 Tiantan Xili, Dongcheng District, 100050, Beijing, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: Beijing Neurosurgical Institute, No. 6 Tiantan Xili, Dongcheng District, 100050, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tiantan Xili, Dongcheng District, 100050, Beijing, China; China National Clinical Research Center for Neurological Diseases, No.6 Tiantan Xili, Dongcheng District, 100050, Beijing, China; Center of Brain Tumor, Beijing Institute for Brain Disorders, No.6 Tiantan Xili, Dongcheng District, 100050, Beijing, China. Electronic address: taojiang1964@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D044466:Asian People / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002681:China; D022001:Focal Adhesions / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D005909:Glioblastoma / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human
keywords: Cell migration; GBM; HIF-1α; IDH1 mutation