Dataset Information

Timing gone awry: distinct tumour suppressive and oncogenic roles of the circadian clock and crosstalk with hypoxia signalling in diverse malignancies.

ABSTRACT:

Background

The circadian clock governs a large variety of fundamentally important physiological processes in all three domains of life. Consequently, asynchrony in timekeeping mechanisms could give rise to cellular dysfunction underpinning many disease pathologies including human neoplasms. Yet, detailed pan-cancer evidence supporting this notion has been limited.

Methods

In an integrated approach uniting genomic, transcriptomic and clinical data of 21 cancer types (n?=?18,484), we interrogated copy number and transcript profiles of 32 circadian clock genes to identify putative loss-of-function (Clock^Loss) and gain-of-function (Clock^Gain) players. Kaplan-Meier, Cox regression and receiver operating characteristic analyses were employed to evaluate the prognostic significance of both gene sets.

Results

Clock^Loss and Clock^Gain were associated with tumour-suppressing and tumour-promoting roles respectively. Downregulation of Clock^Loss genes resulted in significantly higher mortality rates in five cancer cohorts (n?=?2914): bladder (P?=?0.027), glioma (P?Gain genes had poorer survival outcomes (n?=?2784): glioma (P?Loss genes were negatively correlated with hypoxia inducible factor-1A targets in glioma patients, providing a novel framework for investigating the hypoxia-clock signalling axis.

Conclusions

Loss of timekeeping fidelity promotes tumour progression and influences clinical outcomes. Clock^Loss and Clock^Gain may offer novel druggable targets for improving patient prognosis. Both gene sets can be used for patient stratification in adjuvant chronotherapy treatment. Emerging interactions between the circadian clock and hypoxia may be harnessed to achieve therapeutic advantage using hypoxia-modifying compounds in combination with first-line treatments.

SUBMITTER: Chang WH

PROVIDER: S-EPMC6480786 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Timing gone awry: distinct tumour suppressive and oncogenic roles of the circadian clock and crosstalk with hypoxia signalling in diverse malignancies.

Chang Wai Hoong WH Lai Alvina G AG

Journal of translational medicine 20190423 1

<h4>Background</h4>The circadian clock governs a large variety of fundamentally important physiological processes in all three domains of life. Consequently, asynchrony in timekeeping mechanisms could give rise to cellular dysfunction underpinning many disease pathologies including human neoplasms. Yet, detailed pan-cancer evidence supporting this notion has been limited.<h4>Methods</h4>In an integrated approach uniting genomic, transcriptomic and clinical data of 21 cancer types (n = 18,484), w ...[more]

PMID: 31014368

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Dataset Information

Timing gone awry: distinct tumour suppressive and oncogenic roles of the circadian clock and crosstalk with hypoxia signalling in diverse malignancies.

Background

Methods

Results

Conclusions

Publications

Timing gone awry: distinct tumour suppressive and oncogenic roles of the circadian clock and crosstalk with hypoxia signalling in diverse malignancies.

Similar Datasets

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