4.7 Article

Multi-omics landscape of circadian rhythm pathway alterations in Glioma

Journal

BIOENGINEERED
Volume 12, Issue 1, Pages 3294-3308

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/21655979.2021.1947075

Keywords

Circadian rhythm; prognostic biomarker; multi-omics; bioinformatic analysis

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The circadian rhythm pathway exhibited pathological functions in glioma on a single-gene level. By analyzing multi-omics data, it was found that lower grade glioma (LGG) patients showed higher frequencies of mutations and better survival outcomes related to the circadian rhythm pathway. Quantification of the pathway using a pathway index indicated distinctly altered circadian pathway in LGG patients.
Circadian rhythm pathway was demonstrated pathological functions in glioma on single-gene level. We aim to depict the multi-omics landscape of circadian rhythm pathway alteration in glioma using bioinformatic analyses. Multi-omics data were obtained from cBioPortal database. Comparisons were done regarding clinical parameters, differential-expressed genes and functional annotations. A pathway index was generated using the expression data from TCGA and GTEx to quantify the general alteration level of the pathway with clinical association of circadian rhythm pathway index explored. A total of 30 genes were mapped on the circadian rhythm pathway. Genomic profile ofcircadian rhythm pathway genes exhibited distinct characteristics on multiple levels between lower grade glioma (LGG) and glioblastoma multiforme (GBM) patients. LGG patients presented significantly higher frequencies of multi-omics mutations, as well as significant clinical relevance, on single-gene level. Differential-expressed genes between LGG and GBM patients revealed different functions between subtypes that related to the alteration of circadian rhythm pathway. LGG have significantly higher pathway index than normal brain tissue, while GBM significantly lower than normal tissue (P < 0.01), indicating distinctly altered circadian pathway in LGG. Circadian rhythm pathway index correlated with the prognosis of LGG, but not GBM, patients, with higher score indicating better survival outcome (LGG: HR = 0.39, 95% CI: 0.26 - 0.59, P < 0.001). In conclusion, LGG have more multi-omics alterations of circadian rhythm pathway than GBM. Quantification of circadian rhythm pathway using pathway index demonstrated hyperactivated pathway status in LGG and correlated with the prognosis of LGG patients.

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