A four-gene signature-derived risk score for glioblastoma: prospects for prognostic and response predictive analyses
<b>Objective</b> Glioblastoma (GBM) is the most common primary malignant brain tumor regulated by numerous genes, with poor survival outcomes and unsatisfactory response to therapy. Therefore, a robust, multi-gene signature-derived model is required to predict the prognosis and treatment...
Main Authors: | , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
China Anti-Cancer Association
2019-09-01
|
Series: | Cancer Biology & Medicine |
Subjects: | |
Online Access: | http://www.cancerbiomed.org/index.php/cocr/article/view/1457 |
id |
doaj-882fd41e94bf40198ab694ff3d1896a2 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mianfu Cao Juan Cai Ye Yuan Yu Shi Hong Wu Qing Liu Yueliang Yao Lu Chen Weiqi Dang Xiang Zhang Jingfang Xiao Kaidi Yang Zhicheng He Xiaohong Yao Yonghong Cui Xia Zhang Xiuwu Bian |
spellingShingle |
Mianfu Cao Juan Cai Ye Yuan Yu Shi Hong Wu Qing Liu Yueliang Yao Lu Chen Weiqi Dang Xiang Zhang Jingfang Xiao Kaidi Yang Zhicheng He Xiaohong Yao Yonghong Cui Xia Zhang Xiuwu Bian A four-gene signature-derived risk score for glioblastoma: prospects for prognostic and response predictive analyses Cancer Biology & Medicine Differentially expressed genes gene set enrichment analysis glioblastoma prognosis radiotherapy temozolomide chemotherapy |
author_facet |
Mianfu Cao Juan Cai Ye Yuan Yu Shi Hong Wu Qing Liu Yueliang Yao Lu Chen Weiqi Dang Xiang Zhang Jingfang Xiao Kaidi Yang Zhicheng He Xiaohong Yao Yonghong Cui Xia Zhang Xiuwu Bian |
author_sort |
Mianfu Cao |
title |
A four-gene signature-derived risk score for glioblastoma: prospects for prognostic and response predictive analyses |
title_short |
A four-gene signature-derived risk score for glioblastoma: prospects for prognostic and response predictive analyses |
title_full |
A four-gene signature-derived risk score for glioblastoma: prospects for prognostic and response predictive analyses |
title_fullStr |
A four-gene signature-derived risk score for glioblastoma: prospects for prognostic and response predictive analyses |
title_full_unstemmed |
A four-gene signature-derived risk score for glioblastoma: prospects for prognostic and response predictive analyses |
title_sort |
four-gene signature-derived risk score for glioblastoma: prospects for prognostic and response predictive analyses |
publisher |
China Anti-Cancer Association |
series |
Cancer Biology & Medicine |
issn |
2095-3941 2095-3941 |
publishDate |
2019-09-01 |
description |
<b>Objective</b> Glioblastoma (GBM) is the most common primary malignant brain tumor regulated by numerous genes, with poor survival outcomes and unsatisfactory response to therapy. Therefore, a robust, multi-gene signature-derived model is required to predict the prognosis and treatment response in GBM.<b>Methods</b> Gene expression data of GBM from TCGA and GEO datasets were used to identify differentially expressed genes (DEGs) through DESeq2 or LIMMA methods. The DEGs were then overlapped and used for survival analysis by univariate and multivariate COX regression. Based on the gene signature of multiple survival-associated DEGs, a risk score model was established, and its prognostic and predictive role was estimated through Kaplan–Meier analysis and log-rank test. Gene set enrichment analysis (GSEA) was conducted to explore high-risk score-associated pathways. Western blot was used for protein detection.<b>Results</b> Four survival-associated DEGs of GBM were identified: OSMR, HOXC10, SCARA3, and SLC39A10. The four-gene signature-derived risk score was higher in GBM than in normal brain tissues. GBM patients with a high-risk score had poor survival outcomes. The high-risk group treated with temozolomide chemotherapy or radiotherapy survived for a shorter duration than the low-risk group. GSEA showed that the high-risk score was enriched with pathways such as vasculature development and cell adhesion. Western blot confirmed that the proteins of these four genes were differentially expressed in GBM cells.<b>Conclusions</b> The four-gene signature-derived risk score functions well in predicting the prognosis and treatment response in GBM and will be useful for guiding therapeutic strategies for GBM patients. |
topic |
Differentially expressed genes gene set enrichment analysis glioblastoma prognosis radiotherapy temozolomide chemotherapy |
url |
http://www.cancerbiomed.org/index.php/cocr/article/view/1457 |
work_keys_str_mv |
AT mianfucao afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT juancai afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT yeyuan afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT yushi afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT hongwu afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT qingliu afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT yueliangyao afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT luchen afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT weiqidang afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT xiangzhang afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT jingfangxiao afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT kaidiyang afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT zhichenghe afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT xiaohongyao afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT yonghongcui afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT xiazhang afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT xiuwubian afourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT mianfucao fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT juancai fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT yeyuan fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT yushi fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT hongwu fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT qingliu fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT yueliangyao fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT luchen fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT weiqidang fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT xiangzhang fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT jingfangxiao fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT kaidiyang fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT zhichenghe fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT xiaohongyao fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT yonghongcui fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT xiazhang fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses AT xiuwubian fourgenesignaturederivedriskscoreforglioblastomaprospectsforprognosticandresponsepredictiveanalyses |
_version_ |
1724915264644972544 |
spelling |
doaj-882fd41e94bf40198ab694ff3d1896a22020-11-25T02:11:17ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412095-39412019-09-0116359560510.20892/j.issn.2095-3941.2018.02772018000277A four-gene signature-derived risk score for glioblastoma: prospects for prognostic and response predictive analysesMianfu Cao0Juan Cai1Ye Yuan2Yu Shi3Hong Wu4Qing Liu5Yueliang Yao6Lu Chen7Weiqi Dang8Xiang Zhang9Jingfang Xiao10Kaidi Yang11Zhicheng He12Xiaohong Yao13Yonghong Cui14Xia Zhang15Xiuwu Bian16Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaDepartment of Kidney, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, ChinaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China<b>Objective</b> Glioblastoma (GBM) is the most common primary malignant brain tumor regulated by numerous genes, with poor survival outcomes and unsatisfactory response to therapy. Therefore, a robust, multi-gene signature-derived model is required to predict the prognosis and treatment response in GBM.<b>Methods</b> Gene expression data of GBM from TCGA and GEO datasets were used to identify differentially expressed genes (DEGs) through DESeq2 or LIMMA methods. The DEGs were then overlapped and used for survival analysis by univariate and multivariate COX regression. Based on the gene signature of multiple survival-associated DEGs, a risk score model was established, and its prognostic and predictive role was estimated through Kaplan–Meier analysis and log-rank test. Gene set enrichment analysis (GSEA) was conducted to explore high-risk score-associated pathways. Western blot was used for protein detection.<b>Results</b> Four survival-associated DEGs of GBM were identified: OSMR, HOXC10, SCARA3, and SLC39A10. The four-gene signature-derived risk score was higher in GBM than in normal brain tissues. GBM patients with a high-risk score had poor survival outcomes. The high-risk group treated with temozolomide chemotherapy or radiotherapy survived for a shorter duration than the low-risk group. GSEA showed that the high-risk score was enriched with pathways such as vasculature development and cell adhesion. Western blot confirmed that the proteins of these four genes were differentially expressed in GBM cells.<b>Conclusions</b> The four-gene signature-derived risk score functions well in predicting the prognosis and treatment response in GBM and will be useful for guiding therapeutic strategies for GBM patients.http://www.cancerbiomed.org/index.php/cocr/article/view/1457Differentially expressed genesgene set enrichment analysisglioblastoma prognosisradiotherapytemozolomide chemotherapy |