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Alignment between glioblastoma internal clock and environmental cues ameliorates survival in Drosophila.

ABSTRACT: Virtually every single living organism on Earth shows a circadian (i.e. "approximately a day") internal rhythm that is coordinated with planet rotation (i.e. 24 hours). External cues synchronize the central clock of the organism. Consequences of biological rhythm disruptions have been extensively studied on cancer. Still, mechanisms underlying these alterations, and how they favor tumor development remain largely unknown. Here, we show that glioblastoma-induced neurodegeneration also causes circadian alterations in Drosophila. Preventing neurodegeneration in all neurons by genetic means reestablishes normal biological rhythms. Interestingly, in early stages of tumor development, the central pacemaker lengthens its period, whereas in later stages this is severely disrupted. The re-adjustment of the external light:dark period to longer glioblastoma-induced internal rhythms delays glioblastoma progression and ameliorates associated deleterious effects, even after the tumor onset.

SUBMITTER: Jarabo P

PROVIDER: S-EPMC9247055 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Alignment between glioblastoma internal clock and environmental cues ameliorates survival in Drosophila.

Jarabo Patricia P Barredo Celia G CG de Pablo Carmen C Casas-Tinto Sergio S Martin Francisco A FA

Communications biology 20220630 1

Virtually every single living organism on Earth shows a circadian (i.e. "approximately a day") internal rhythm that is coordinated with planet rotation (i.e. 24 hours). External cues synchronize the central clock of the organism. Consequences of biological rhythm disruptions have been extensively studied on cancer. Still, mechanisms underlying these alterations, and how they favor tumor development remain largely unknown. Here, we show that glioblastoma-induced neurodegeneration also causes circ ...[more]

PMID: 35773327

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Project description:Background: Many biological clocks related to aging have been linked to the development of cancer. A recent study has identified that the inflammatory aging clock was an excellent indicator to track multiple diseases. However, the role of the inflammatory aging clock in glioblastoma (GBM) remains to be explored. This study aimed to investigate the expression patterns and the prognostic values of inflammatory aging (iAge) in GBM, and its relations with stem cells. Methods: Inflammation-related genes (IRG) and their relations with chronological age in normal samples from the Cancer Genome Atlas (TCGA) were identified by the Spearman correlation analysis. Then, we calculated the iAge and computed their correlations with chronological age in 168 patients with GBM. Next, iAge was applied to classify the patients into high- and low-iAge subtypes. Next, the survival analysis was performed. In addition, the correlations between iAge and stem cell indexes were evaluated. Finally, the results were validated in an external cohort. Results: Thirty-eight IRG were significantly associated with chronological age (|coefficient| > 0.5), and were used to calculate the iAge. Correlation analysis showed that iAge was positively correlated with chronological age. Enrichment analysis demonstrated that iAge was highly associated with immune cells and inflammatory activities. Survival analysis showed the patients in the low-iAge subtype had significantly better overall survival (OS) than those in the high-iAge subtype (p < 0.001). In addition, iAge outperformed the chronological age in revealing the correlations with stem cell stemness. External validation demonstrated that iAge was an excellent method to classify cancer subtypes and predict survival in patients with GBM. Conclusions: Inflammatory aging clock may be involved in the GBM via potential influences on immune-related activities. iAge could be used as biomarkers for predicting the OS and monitoring the stem cell.

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Dataset Information

Alignment between glioblastoma internal clock and environmental cues ameliorates survival in Drosophila.

Publications

Alignment between glioblastoma internal clock and environmental cues ameliorates survival in Drosophila.

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