Integrated analysis of single‐cell RNA‐seq dataset and bulk RNA‐seq dataset constructs a prognostic model for predicting survival in human glioblastoma

Abstract Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. For patients with GBM, the median overall survival (OS) is 14.6 months and the 5‐year survival rate is 7.2%. It is imperative to develop a reliable model to predict the survival probability in new GBM...

Full description

Bibliographic Details
Main Authors: Wenwen Lai, Defu Li, Jie Kuang, Libin Deng, Quqin Lu
Format: Article
Language:English
Published: Wiley 2022-05-01
Series:Brain and Behavior
Subjects:
Online Access:https://doi.org/10.1002/brb3.2575
_version_ 1797737292210634752
author Wenwen Lai
Defu Li
Jie Kuang
Libin Deng
Quqin Lu
author_facet Wenwen Lai
Defu Li
Jie Kuang
Libin Deng
Quqin Lu
author_sort Wenwen Lai
collection DOAJ
description Abstract Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. For patients with GBM, the median overall survival (OS) is 14.6 months and the 5‐year survival rate is 7.2%. It is imperative to develop a reliable model to predict the survival probability in new GBM patients. To date, most prognostic models for predicting survival in GBM were constructed based on bulk RNA‐seq dataset, which failed to accurately reflect the difference between tumor cores and peripheral regions, and thus show low predictive capability. An effective prognostic model is desperately needed in clinical practice. Methods We studied single‐cell RNA‐seq dataset and The Cancer Genome Atlas‐glioblastoma multiforme (TCGA‐GBM) dataset to identify differentially expressed genes (DEGs) that impact the OS of GBM patients. We then applied the least absolute shrinkage and selection operator (LASSO) Cox penalized regression analysis to determine the optimal genes to be included in our risk score prognostic model. Then, we used another dataset to test the accuracy of our risk score prognostic model. Results We identified 2128 DEGs from the single‐cell RNA‐seq dataset and 6461 DEGs from the bulk RNA‐seq dataset. In addition, 896 DEGs associated with the OS of GBM patients were obtained. Five of these genes (LITAF, MTHFD2, NRXN3, OSMR, and RUFY2) were selected to generate a risk score prognostic model. Using training and validation datasets, we found that patients in the low‐risk group showed better OS than those in the high‐risk group. We validated our risk score model with the training and validating datasets and demonstrated that it can effectively predict the OS of GBM patients. Conclusion We constructed a novel prognostic model to predict survival in GBM patients by integrating a scRNA‐seq dataset and a bulk RNA‐seq dataset. Our findings may advance the development of new therapeutic targets and improve clinical outcomes for GBM patients.
first_indexed 2024-03-12T13:26:33Z
format Article
id doaj.art-7c807b440c2a40419057c081d1232d0e
institution Directory Open Access Journal
issn 2162-3279
language English
last_indexed 2024-03-12T13:26:33Z
publishDate 2022-05-01
publisher Wiley
record_format Article
series Brain and Behavior
spelling doaj.art-7c807b440c2a40419057c081d1232d0e2023-08-25T04:42:55ZengWileyBrain and Behavior2162-32792022-05-01125n/an/a10.1002/brb3.2575Integrated analysis of single‐cell RNA‐seq dataset and bulk RNA‐seq dataset constructs a prognostic model for predicting survival in human glioblastomaWenwen Lai0Defu Li1Jie Kuang2Libin Deng3Quqin Lu4Jiangxi Provincial Key Laboratory of Preventive Medicine Nanchang University Nanchang ChinaJiangxi Provincial Key Laboratory of Preventive Medicine Nanchang University Nanchang ChinaJiangxi Provincial Key Laboratory of Preventive Medicine Nanchang University Nanchang ChinaJiangxi Provincial Key Laboratory of Preventive Medicine Nanchang University Nanchang ChinaJiangxi Provincial Key Laboratory of Preventive Medicine Nanchang University Nanchang ChinaAbstract Background Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. For patients with GBM, the median overall survival (OS) is 14.6 months and the 5‐year survival rate is 7.2%. It is imperative to develop a reliable model to predict the survival probability in new GBM patients. To date, most prognostic models for predicting survival in GBM were constructed based on bulk RNA‐seq dataset, which failed to accurately reflect the difference between tumor cores and peripheral regions, and thus show low predictive capability. An effective prognostic model is desperately needed in clinical practice. Methods We studied single‐cell RNA‐seq dataset and The Cancer Genome Atlas‐glioblastoma multiforme (TCGA‐GBM) dataset to identify differentially expressed genes (DEGs) that impact the OS of GBM patients. We then applied the least absolute shrinkage and selection operator (LASSO) Cox penalized regression analysis to determine the optimal genes to be included in our risk score prognostic model. Then, we used another dataset to test the accuracy of our risk score prognostic model. Results We identified 2128 DEGs from the single‐cell RNA‐seq dataset and 6461 DEGs from the bulk RNA‐seq dataset. In addition, 896 DEGs associated with the OS of GBM patients were obtained. Five of these genes (LITAF, MTHFD2, NRXN3, OSMR, and RUFY2) were selected to generate a risk score prognostic model. Using training and validation datasets, we found that patients in the low‐risk group showed better OS than those in the high‐risk group. We validated our risk score model with the training and validating datasets and demonstrated that it can effectively predict the OS of GBM patients. Conclusion We constructed a novel prognostic model to predict survival in GBM patients by integrating a scRNA‐seq dataset and a bulk RNA‐seq dataset. Our findings may advance the development of new therapeutic targets and improve clinical outcomes for GBM patients.https://doi.org/10.1002/brb3.2575glioblastomaoverall survivalprognostic modelsingle‐cell RNA‐seqbulk RNA‐seq
spellingShingle Wenwen Lai
Defu Li
Jie Kuang
Libin Deng
Quqin Lu
Integrated analysis of single‐cell RNA‐seq dataset and bulk RNA‐seq dataset constructs a prognostic model for predicting survival in human glioblastoma
Brain and Behavior
glioblastoma
overall survival
prognostic model
single‐cell RNA‐seq
bulk RNA‐seq
title Integrated analysis of single‐cell RNA‐seq dataset and bulk RNA‐seq dataset constructs a prognostic model for predicting survival in human glioblastoma
title_full Integrated analysis of single‐cell RNA‐seq dataset and bulk RNA‐seq dataset constructs a prognostic model for predicting survival in human glioblastoma
title_fullStr Integrated analysis of single‐cell RNA‐seq dataset and bulk RNA‐seq dataset constructs a prognostic model for predicting survival in human glioblastoma
title_full_unstemmed Integrated analysis of single‐cell RNA‐seq dataset and bulk RNA‐seq dataset constructs a prognostic model for predicting survival in human glioblastoma
title_short Integrated analysis of single‐cell RNA‐seq dataset and bulk RNA‐seq dataset constructs a prognostic model for predicting survival in human glioblastoma
title_sort integrated analysis of single cell rna seq dataset and bulk rna seq dataset constructs a prognostic model for predicting survival in human glioblastoma
topic glioblastoma
overall survival
prognostic model
single‐cell RNA‐seq
bulk RNA‐seq
url https://doi.org/10.1002/brb3.2575
work_keys_str_mv AT wenwenlai integratedanalysisofsinglecellrnaseqdatasetandbulkrnaseqdatasetconstructsaprognosticmodelforpredictingsurvivalinhumanglioblastoma
AT defuli integratedanalysisofsinglecellrnaseqdatasetandbulkrnaseqdatasetconstructsaprognosticmodelforpredictingsurvivalinhumanglioblastoma
AT jiekuang integratedanalysisofsinglecellrnaseqdatasetandbulkrnaseqdatasetconstructsaprognosticmodelforpredictingsurvivalinhumanglioblastoma
AT libindeng integratedanalysisofsinglecellrnaseqdatasetandbulkrnaseqdatasetconstructsaprognosticmodelforpredictingsurvivalinhumanglioblastoma
AT quqinlu integratedanalysisofsinglecellrnaseqdatasetandbulkrnaseqdatasetconstructsaprognosticmodelforpredictingsurvivalinhumanglioblastoma