Genomics and Prognosis Analysis of Epithelial-Mesenchymal Transition in Glioma

被引:64
作者
Tao, Chuming [1 ,2 ]
Huang, Kai [1 ]
Shi, Jin [1 ]
Hu, Qing [1 ,2 ]
Li, Kuangxun [3 ]
Zhu, Xingen [1 ]
机构
[1] Nanchang Univ, Dept Neurosurg, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China
[2] East China Inst Digital Med Engn, Sci Res Ctr, Shangrao, Peoples R China
[3] Nanchang Univ, Jiangxi Med Coll, Queen Mary Sch, Nanchang, Jiangxi, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2020年 / 10卷
关键词
gene expression profile; glioma; epithelial-mesenchymal transition epigenetics; prognostic signature; overall survival; GLIOBLASTOMA-MULTIFORME; SIGNALING PATHWAY; CANCER; SNAIL; INVASION; CELLS; SLUG; ACTIVATION; SURVIVAL; CADHERIN;
D O I
10.3389/fonc.2020.00183
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Epithelial-mesenchymal transition (EMT) is regulated by induction factors, transcription factor families and an array of signaling pathways genes, and has been implicated in the invasion and progression of gliomas. Methods: We obtained the Clinicopathological data sets from Chinese Glioma Genome Atlas (CGGA). The "limma" package was used to analyze the expression of EMT-related genes in gliomas with different pathological characteristics. We used the "ConsensusClusterPlus" package to divide gliomas into two groups to study their correlation with glioma malignancy. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to select seven prognosis-associated genes to build the risk signature, and the coefficients obtained from the LASSO algorithm were used to calculate the risk score which we applied to determine the prognostic value of the risk signature. Univariate and multivariate Cox regression analyses were used to determine whether the risk signature is an independent prognostic indicator. Results: We analyzed the differentially expressed 22 common epithelial-mesenchymal transition-associated genes in 508 gliomas graded by different clinicopathological features. Two glioma subgroups (EM1/2) were identified by consistent clustering of the proteins, of which the EM1 subgroup had a better prognosis than the EM2 subgroup, and the EM2 group was associated with cancer migration and proliferation. Significant enrichment analysis revealed that EMT-related transcriptional regulators and signaling pathways genes were highly related to glioma malignancies. Seven EMT-related genes were used to derive risk scores, which served as independent prognostic markers and prediction factors for the clinicopathological features of glioma. And we found the overall survival (OS) was significantly different between the low- and high-risk groups, the ROC curve indicated that the risk score can predict survival rates for glioma patients. Conclusion: EMT-related induction factors, transcriptional regulators and signaling pathways genes are important players in the malignant progression of glioma and may help in decision making regarding the choice of prognosis assessment and provide us clues to understand EMT epigenetic modification in glioma.
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页数:13
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  • [1] The Snail genes as inducers of cell movement and survival: implications in development and cancer
    Barrallo-Gimeno, A
    Nieto, MA
    [J]. DEVELOPMENT, 2005, 132 (14): : 3151 - 3161
  • [2] Predicting survival from microarray data -: a comparative study
    Bovelstad, H. M.
    Nygard, S.
    Storvold, H. L.
    Aldrin, M.
    Borgan, O.
    Frigessi, A.
    Lingjaerde, O. C.
    [J]. BIOINFORMATICS, 2007, 23 (16) : 2080 - 2087
  • [3] Snail and slug play distinct roles during breast carcinoma progression
    Come, Christophe
    Magnino, Fabrice
    Bibeau, Frederic
    Barbara, Pascal De Santa
    Becker, Karl Friedrich
    Theillet, Charles
    Savagner, Pierre
    [J]. CLINICAL CANCER RESEARCH, 2006, 12 (18) : 5395 - 5402
  • [4] Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features
    Creighton, Chad J.
    Li, Xiaoxian
    Landis, Melissa
    Dixon, J. Michael
    Neumeister, Veronique M.
    Sjolund, Ashley
    Rimm, David L.
    Wong, Helen
    Rodriguez, Angel
    Herschkowitz, Jason I.
    Fan, Cheng
    Zhang, Xiaomei
    He, Xiaping
    Pavlick, Anne
    Gutierrez, M. Carolina
    Renshaw, Lorna
    Larionov, Alexey A.
    Faratian, Dana
    Hilsenbeck, Susan G.
    Perou, Charles M.
    Lewis, Michael T.
    Rosen, Jeffrey M.
    Chang, Jenny C.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (33) : 13820 - 13825
  • [5] Signaling pathway cooperation in TGF-β-induced epithelial-mesenchymal transition
    Derynck, Rik
    Muthusamy, Baby Periyanayaki
    Saeteurn, Koy Y.
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2014, 31 : 56 - 66
  • [6] Dragomirescu M, 2018, ROM J MORPHOL EMBRYO, V59, P131
  • [7] Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms
    Elinav, Eran
    Nowarski, Roni
    Thaiss, Christoph A.
    Hu, Bo
    Jin, Chengcheng
    Flavell, Richard A.
    [J]. NATURE REVIEWS CANCER, 2013, 13 (11) : 759 - 771
  • [8] Snail, slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma
    Elloul, S
    Elstrand, MB
    Nesland, JM
    Tropé, CG
    Kvalheim, G
    Goldberg, I
    Reich, R
    Davidson, B
    [J]. CANCER, 2005, 103 (08) : 1631 - 1643
  • [9] Hepatocyte growth factor induces cell scattering through MAPK/Egr-1-mediated upregulation of Snail
    Grotegut, Stefan
    von Schweinitz, Dietrich
    Christofori, Gerhard
    Lehembre, Francois
    [J]. EMBO JOURNAL, 2006, 25 (15) : 3534 - 3545
  • [10] CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks
    Guo, F.
    Wang, Y.
    Liu, J.
    Mok, S. C.
    Xue, F.
    Zhang, W.
    [J]. ONCOGENE, 2016, 35 (07) : 816 - 826