Open AccessCircadian clock genes promote glioma progression by affecting tumour immune infiltration and tumour cell proliferation
Author(s) -
Wang Zeyu,
Su Guanhua,
Dai Ziyu,
Meng Ming,
Zhang Hao,
Fan Fan,
Liu Zhengzheng,
Zhang Longbo,
Weygant Nathaniel,
He Fengqiong,
Fang Ning,
Zhang Liyang,
Cheng Quan
Publication year - 2021
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12988
Subject(s) - circadian rhythm , biology , circadian clock , cell cycle , immune system , glioma , timeless , cancer research , gene , gene expression , flow cytometry , cell , clock , immunology , genetics , neuroscience
Objectives Circadian rhythm controls complicated physiological activities in organisms. Circadian clock genes have been related to tumour progression, but its role in glioma is unknown. Therefore, we explored the relationship between dysregulated circadian clock genes and glioma progression. Materials and Methods Samples were divided into different groups based on circadian clock gene expression in training dataset (n = 672) and we verified the results in other four validating datasets (n = 1570). The GO and GSEA enrichment analysis were conducted to explore potential mechanism of how circadian clock genes affected glioma progression. The single‐cell RNA‐Seq analysis was conducted to verified previous results. The immune landscape was evaluated by the ssGSEA and CIBERSORT algorithm. Cell proliferation and viability were confirmed by the CCK8 assay, colony‐forming assay and flow cytometry. Results The cluster and risk model based on circadian clock gene expression can predict survival outcome. Samples were scoring by the least absolute shrinkage and selection operator regression analysis, and high scoring tumour was associated with worse survival outcome. Samples in high‐risk group manifested higher activation of immune pathway and cell cycle. Tumour immune landscape suggested high‐risk tumour infiltrated more immunocytes and more sensitivity to immunotherapy. Interfering TIMELESS expression affected circadian clock gene expression, inhibited tumour cell proliferation and arrested cell cycle at the G0/G1 phase. Conclusions Dysregulated circadian clock gene expression can affect glioma progression by affecting tumour immune landscape and cell cycle. The risk model can predict glioma survival outcome, and this model can also be applied to pan‐cancer.