Multi-omics landscape of circadian rhythm pathway alterations in Glioma

ABSTRACT

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.

Graphical abstract

KEYWORDS:

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

Highlights

1. Circadian rhythm pathway has higher frequencies of mutations in LGG than GBM;

2. Alterations in circadian rhythm pathway correlate with the prognosis of LGG patients;

3. Circadian rhythm pathway index can be used to quantify general alterations of the pathway;

4. Circadian rhythm pathway index significantly correlated with the prognosis of LGG patients.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Consent for publication

All authors have read the manuscript and approve for publication.

Authors’ contributions

CZ and JX completed the analysis and drafted the manuscript; LC participated in the figure illustration and codes; XC designed the study and took responsibility for further contact.

Data availability statement

The datasets generated and/or analysed during the current study are available in the UCSC XENA repository, [https://tcga.xenahubs.net]. Data used included the Cancer Genome Atlas (TCGA, http://can‑cergenome.nih.gov/), the GTEx projects.

Supplementary material

Supplemental data for this article can be accessed here.