CDH6 as a prognostic indicator and marker for chemotherapy in gliomas

Ming Meng; Ming Meng; Hongshu Zhou; Hongshu Zhou; Ye He; Ye He; Ye He; Lu Chen; Lu Chen; Lu Chen; Wanpeng Wang; Wanpeng Wang; Wanpeng Wang; Liting Yang; Liting Yang; Liting Yang; Zeyu Wang; Zeyu Wang; Liyang Zhang; Liyang Zhang; Liyang Zhang; Sha Wang; Sha Wang; Sha Wang

doi:10.3389/fgene.2022.949552

Frontiers in Genetics (Jul 2022)

CDH6 as a prognostic indicator and marker for chemotherapy in gliomas

Ming Meng,
Ming Meng,
Hongshu Zhou,
Hongshu Zhou,
Ye He,
Ye He,
Ye He,
Lu Chen,
Lu Chen,
Lu Chen,
Wanpeng Wang,
Wanpeng Wang,
Wanpeng Wang,
Liting Yang,
Liting Yang,
Liting Yang,
Zeyu Wang,
Zeyu Wang,
Liyang Zhang,
Liyang Zhang,
Liyang Zhang,
Sha Wang,
Sha Wang,
Sha Wang

Affiliations

Ming Meng: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Ming Meng: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Hongshu Zhou: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Hongshu Zhou: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Ye He: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Ye He: Eye Center of Xiangya Hospital, Central South University, Changsha, China
Ye He: Hunan Key Laboratory of Ophthalmology, Changsha, China
Lu Chen: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Lu Chen: Eye Center of Xiangya Hospital, Central South University, Changsha, China
Lu Chen: Hunan Key Laboratory of Ophthalmology, Changsha, China
Wanpeng Wang: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Wanpeng Wang: Eye Center of Xiangya Hospital, Central South University, Changsha, China
Wanpeng Wang: Hunan Key Laboratory of Ophthalmology, Changsha, China
Liting Yang: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Liting Yang: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Liting Yang: Clinical Diagnosis and Therapy Center for Glioma, Xiangya Hospital, Central South University, Changsha, China
Zeyu Wang: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Zeyu Wang: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Liyang Zhang: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
Liyang Zhang: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Liyang Zhang: Clinical Diagnosis and Therapy Center for Glioma, Xiangya Hospital, Central South University, Changsha, China
Sha Wang: National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
Sha Wang: Eye Center of Xiangya Hospital, Central South University, Changsha, China
Sha Wang: Hunan Key Laboratory of Ophthalmology, Changsha, China

DOI: https://doi.org/10.3389/fgene.2022.949552
Journal volume & issue: Vol. 13

Abstract

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Glioma is the most malignant cancer of the central nervous system. There are various therapies for treating gliomas, but their outcomes are not satisfactory. Therefore, new targets for glioma treatment are needed. This study examined the cadherin-6 (CDH6) expression in gliomas using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. CDH6 expression positively correlated with the World Health Organization (WHO) tumor grade and negatively correlated with patient prognosis. A significant decrease in CDH6 promoter methylation was identified with an increase in the WHO grade severity. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that CDH6 might be involved in cell–cell interactions and immune processes in the glioma microenvironment. Weighted gene co-expression network analysis revealed a correlation between CDH6 and cell adhesion molecules, focal adhesions, phosphatidylinositol 3-kinase-protein kinase B signaling pathways, nuclear division, chromosome segregation, mitotic nuclear division, and immune-related pathways. CDH6 strongly correlated with immunosuppressive cells, including regulatory T cells, monocytes, macrophages, tumor-associated macrophages, and myeloid-derived suppressor cells. It also showed correlations with immune-active cells such as B cells, CD8+ T cells, and dendritic cells. Single-cell analysis showed that CDH6 was expressed mainly in astrocyte (AC)-like malignant cells. Differentially expressed genes of AC-like malignant cells were found to be associated with stress response, membranous processes, viral infections, and several types of cancers. Potential drugs associated with high CDH6 expression were also predicted, including AMG-22, rutin, CCT128930, deforolimus, bis(maltolato)oxovanadium, anagrelide, vemurafenib, CHIR-98014, and AZD5582. Thus, this study showed that CDH6 correlates with glioma immune infiltration, it is expressed mainly in AC-like malignant cells, and it may act as a new target for glioma therapy.

Published in Frontiers in Genetics

ISSN: 1664-8021 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Genetics
Website: http://journal.frontiersin.org/journal/genetics

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