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Research Paper|Volume 13, Issue 5|pp 6662—6680

The novel roles of virus infection-associated gene CDKN1A in chemoresistance and immune infiltration of glioblastoma

Kuan Hu1, Juanni Li2, Geting Wu2, Lei Zhou3, Xiang Wang4, Yuanliang Yan4,5, Zhijie Xu2,5
  • 1Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
  • 2Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
  • 3Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410008, Hunan, China
  • 4Department of Pharmacy, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
  • 5National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
* Equal contribution
Received: July 16, 2020Accepted: December 29, 2020Published: February 17, 2021
https://doi.org/10.18632/aging.202519

Copyright: © 2021 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Chemoresistance is a common limitation for successful treatment of glioblastoma multiforme (GBM). Recently, virus infections have been demonstrated to be associated with tumorigenesis and chemoresistance in tumors. However, the role of infection-related genes in GBM haven’t been clearly demonstrated. Here, we explored the roles and mechanisms of human T-lymphotropic virus type-1 (HTLV-1) infections in tumorigenesis and chemoresistance in GBM. Four candidate genes, CDKN1A, MSX1, MYC and CHEK2, were identified to be the codifferentially expressed genes between three temozolomide (TMZ) chemotherapy datasets and one HTLV-1 infection gene set. Next, comprehensive bioinformatics data from several databases indicated that only CDKN1A was significantly upregulated in both GBM tissues and cells and showed the greatest prognostic value in GBM patients. Clinical data identified the correlations between CDKN1A expression and clinicopathological parameters of GBM patients. Moreover, CDKN1A was found to be involved in AKT-mediated TMZ resistance of glioma cells. In addition, KEGG analysis of CDKN1A-associated coexpression genes showed that CDKN1A was potentially involved in complement and coagulation cascades pathways in GBM. Finally, TISIDB database was used to investigate the role of CDKN1A in tumor-immune system interactions in GBM. These findings enhanced our understanding of the roles of CDKN1A in tumorigenesis and therapy response in GBM.