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pmid:33101383
Identification of a Twelve-Gene Signature and Establishment of a Prognostic Nomogram Predicting Overall Survival for Medulloblastoma.
Sihan Zhu · Fuhua Lin · Zhenghe Chen · Xiaobing Jiang · Ji Zhang · Qunying Yang · Yinsheng Chen · Jian Wang
Frontiers in genetics · 2020 doi:10.3389/fgene.2020.563882
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Complete file
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To provide patients with more clinically beneficial treatment strategies, there is a pressing need to develop a new prognostic prediction model as a supplement to the prediction outcomes of clinical judgment.\nMATERIALS AND METHODS: Four datasets of mRNA expression and clinical data were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and functionally enriched among GSE50161, GSE74195, GSE86574. Then we used STRING and Cytoscape to constructed and analyze protein-protein interaction network (PPI) and hub genes. Univariate cox regression analysis was performed to identify overall survival-related hub genes in an unique dataset from GSE85217 as train cohort. Lasso Cox regression model was used to construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier curve, univariate and multivariate Cox regression analysis were used to assess the prognostic capacity of the twelve-gene signature. A unique dataset from GSE85217 was downloaded to further validate the results. Finally, we established the nomogram by using the gene signature and validated it with ROC curve. Gene set enrichment analysis (GSEA) was carried out to further investigate its potential molecular mechanism. Besides, the twelve genes expression at the mRNA and protein levels was validated using external database such as Oncomine, cBioportal and HPA, respectively.\nRESULTS: A twelve-gene signature comprising FOXM1, NEK2, CCT2, ACTL6A, EIF4A3, CCND2, ABL1, SYNCRIP, ITGB1, NRXN2, ENAH, and UMPS was established to predict overall survival of medulloblastoma. The ROC curve showed good performance in survival prediction in both the train cohort and the validation cohort. The twelve-gene signature could stratify patients into a high risk and low risk group which had significantly different survival. Univariate and multivariate Cox regression revealed that the twelve-gene signature was an independent prognostic factor in medulloblastoma. Nomogram, which included twelve-gene signatures, was established and showed some clinical benefit.\nCONCLUSION: Our study identified a twelve-gene signature and established a prognostic nomogram that reliably predicts overall survival in medulloblastoma. The above results will help us to better analyze the pathogenesis and treatment of medulloblastoma in the future.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate cox regression analysis were used to assess whether the prognostic model could be independent of other clinicopathological factors (including age, gender, histology, metastasis staging, molecular subgroup and risk score) (Table 2) for MB patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33101383", "locator": "sections[8] \"Prognostic Model Based on Gene Signature as an Independent Predictor for OS and Validation by Using Multiple Databases\" paragraph 2", "quote": "Univariate and multivariate cox regression analysis were used to assess whether the prognostic model could be independent of other clinicopathological factors (including age, gender, histology, metastasis staging, molecular subgroup and risk score) (Table 2) for MB patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. 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"taxon": "Homo sapiens", "title": "Expression data from primary medulloblastoma samples", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE86217", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE86217", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE86217", "version": null, "note": "Publicly available datasets were analyzed in this study. 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"[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array", "31 (26/5)", "Identification of DEGs"], ["GSE50161", "Griesinger et al., 2013", "[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array", "35 (22/13)", "Identification of DEGs"], ["GSE86574", "Amani et al., 2017", "[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array", "27 (17/10)", "Identification of DEGs"], ["GSE85217", "Florence et al., 2017", "[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version]", "532 (532/0)", "Construction signature and validation"]], "row_count": 5, "column_count": 5, "numeric_cells": 16, "header_rows": 1, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33101383:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:18ddb550b2b2b532117ab853742f8e8760b3ccb63549da1a14f516d3fc0db554", "bytes": 732, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[8]/table-wrap[1]#T2", "version": null, "note": "Summary of clinical data.", "structure": {"pmcid": "PMC7495025", "section_index": 8, "section_title": "Prognostic Model Based on Gene Signature as an Independent Predictor for OS and Validation by Using Multiple Databases", "row_count": 22, "column_count": 3}, "table": {"label": "TABLE 2", "caption": "Summary of clinical data.", "rows": [["", "Train cohort", "Validation cohort"], ["Case included (n)", "323", "109"], ["Age (mean ± SD)", "5.4 (± 8.06)", "8.6 (± 7.39)"], ["Overall survival", "", ""], ["Year (mean ± SD)", "3.2 (± 5.13)", "2.4 (± 3.31)"], ["Status (alive/dead)", "204/119", "67/42"], ["Gender", "", ""], ["Male", "205", "73"], ["Female", "118", "36"], ["Histology", "", ""], ["Classic", "237", "55"], ["Des", "40", "29"], ["LCA", "38", "19"], ["MBEN", "8", "6"], ["Subgroup", "", ""], ["WNT", "29", "6"], ["SHH", "86", "36"], ["Group3", "156", "29"], ["Group4", "52", "38"], ["Metastasis", "", ""], ["M0", "222", "81"], ["M1", "101", "28"]], "row_count": 22, "column_count": 3, "numeric_cells": 32, "header_rows": 1, "locator": "section[8]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:33101383:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:73d1e1b65e1e1320d267b15660377b76081f5290a041982349b8afe831c4ce5a", "bytes": 1401, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#T3", "version": null, "note": "Functional roles of twelve genes.", "structure": {"pmcid": "PMC7495025", "section_index": 14, "section_title": "Identification of Survival-Related Hub Genes and Establishment of the Twelve-Gene Prognostic Signature", "row_count": 13, "column_count": 3}, "table": {"label": "TABLE 3", "caption": "Functional roles of twelve genes.", "rows": [["Gene symbol", "Full name", "Function"], ["FOXM1", "Forkhead box M1", "A transcriptional activator involved in cell proliferation."], ["NEK2", "NIMA related kinase 2", "A serine/threonine-protein kinase that is involved in mitotic regulation"], ["CCT2", "Chaperonin containing TCP1 subunit 2", "A molecular chaperone that is a member of the chaperonin containing TCP1 complex"], ["ACTL6A", "Actin like 6A", "A family member of actin-related proteins"], ["E1F4A3", "Eukaryotic translation initiation factor 4A3", "A member of the DEAD box protein family"], ["CCND2", "Cyclin D2", "A dramatic periodicity in protein abundance through the cell cycle"], ["ABL1", "ABL proto-oncogene 1, non-receptor tyrosine kinase", "A protein tyrosine kinase involved in a variety of cellular processes"], ["SYNCRIP", "Synaptotagmin binding cytoplasmic RNA interacting protein", "A member of the cellular heterogeneous nuclear ribonucleoprotein"], ["ITGB1", "Integrin subunit beta 1", "This gene encodes a beta subunit"], ["NRXN2", "Neurexin 2", "A member of the neurexin gene family"], ["ENAH", "ENAH actin regulator", "Members of this gene family are involved in actin-based motility."], ["UMPS", "Uridine monophosphate synthetase", "A uridine 5′-monophosphate synthase"]], "row_count": 13, "column_count": 3, "numeric_cells": 8, "header_rows": 1, "locator": "section[14]/table-wrap[1]#T3"}}], "gaps": ["asset:data:geo:GSE50161 not downloaded", "asset:data:geo:GSE50161 licence not read", "asset:data:geo:GSE74195 not downloaded", "asset:data:geo:GSE74195 licence not read", "asset:data:geo:GSE85217 not downloaded", "asset:data:geo:GSE85217 licence not read", "asset:data:geo:GSE86217 not downloaded", "asset:data:geo:GSE86217 licence not read", "asset:data:geo:GSE86574 not downloaded", "asset:data:geo:GSE86574 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": 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