Prognostic Prediction Model for Glioblastoma: A Metabolic Gene Signature and Independent External Validation

Lei, Chuxiang; Chen, Wenlin; Wang, Yuekun; Zhao, Binghao; Liu, Penghao; Kong, Ziren; Liu, Delin; Dai, Congxin; Wang, Yaning; Wang, Yu; Ma, Wenbin

doi:10.7150/jca.53827

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J Cancer 2021; 12(13):3796-3808. doi:10.7150/jca.53827 This issue Cite

Research Paper

Prognostic Prediction Model for Glioblastoma: A Metabolic Gene Signature and Independent External Validation

Chuxiang Lei, B.S.^1*, Wenlin Chen, B.S.^2*, Yuekun Wang, B.S.², Binghao Zhao, M.D.², Penghao Liu, B.S.², Ziren Kong, B.S.², Delin Liu, B.S.², Congxin Dai, M.D.², Yaning Wang, M.D.², Yu Wang, M.D.^2✉, Wenbin Ma, M.D.^2✉

1. Department of Vascular Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China.
2. Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China.
*These authors contributed equally to this work.

✉ Corresponding authors: Yu Wang, Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China. Tel.: +8615311860318, Fax More

Citation:

Lei C, Chen W, Wang Y, Zhao B, Liu P, Kong Z, Liu D, Dai C, Wang Y, Wang Y, Ma W. Prognostic Prediction Model for Glioblastoma: A Metabolic Gene Signature and Independent External Validation. J Cancer 2021; 12(13):3796-3808. doi:10.7150/jca.53827. https://www.jcancer.org/v12p3796.htm

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Abstract

Background: Glioblastoma (GBM) is the most common primary malignant intracranial tumor and closely related to metabolic alteration. However, few accepted prognostic models are currently available, especially models based on metabolic genes.

Methods: The transcriptome data were obtained for all of the patients diagnosed with GBM from the Gene Expression Omnibus (GEO) (training cohort, n=369) and The Cancer Genome Atlas (TCGA) (validation cohort, n=152) with the following variables: age at diagnosis, sex, follow-up and overall survival (OS). Metabolic genes according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were contracted, and a Lasso regression model was constructed. Survival was assessed by univariate or multivariate Cox proportional hazards regression and Kaplan-Meier analysis, and an independent external validation was also conducted to examine the model.

Results: There were 341 metabolic genes showed significant differences between normal brain and GBM tissues in both the training and validation cohorts, among which 56 genes were dramatically correlated to the OS of patients. Lasso regression revealed that the metabolic prognostic model was composed of 18 genes, including COX10, COMT, and GPX2 with protective effects, as well as OCRL and RRM2 with unfavorable effects. Patients classified as high-risk by the risk score from this model had markedly shorter OS than low-risk patients (P<0.0001), and this significant result was also observed in independent external validation (P<0.001).

Conclusions: The prognosis of GBM was dramatically related to metabolic pathways, and our metabolic prognostic model had high accuracy and application value in predicting the OS of GBM patients.

Keywords: glioblastoma, metabolic gene, prognostic model, GEO, TCGA

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APA

Lei, C., Chen, W., Wang, Y., Zhao, B., Liu, P., Kong, Z., Liu, D., Dai, C., Wang, Y., Wang, Y., Ma, W. (2021). Prognostic Prediction Model for Glioblastoma: A Metabolic Gene Signature and Independent External Validation. Journal of Cancer, 12(13), 3796-3808. https://doi.org/10.7150/jca.53827.

ACS

Lei, C.; Chen, W.; Wang, Y.; Zhao, B.; Liu, P.; Kong, Z.; Liu, D.; Dai, C.; Wang, Y.; Wang, Y.; Ma, W. Prognostic Prediction Model for Glioblastoma: A Metabolic Gene Signature and Independent External Validation. J. Cancer 2021, 12 (13), 3796-3808. DOI: 10.7150/jca.53827.

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CSE

Lei C, Chen W, Wang Y, Zhao B, Liu P, Kong Z, Liu D, Dai C, Wang Y, Wang Y, Ma W. 2021. Prognostic Prediction Model for Glioblastoma: A Metabolic Gene Signature and Independent External Validation. J Cancer. 12(13):3796-3808.

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