Genes Relevant to Tissue Response to Cancer Therapy Display Diurnal Variation in mRNA Expression in Human Oral Mucosa

Area of Science:

• Chronobiology
• Cancer Therapeutics
• Molecular Biology

Background:

• Cancer chronotherapy requires precise treatment timing for individual patients.
• Oral mucosa is susceptible to damage from cancer therapies, necessitating research into its diurnal variations.
• Understanding gene expression patterns in oral tissue is critical for optimizing treatment schedules.

Purpose of the Study:

• To characterize diurnal variations in gene expression within oral mucosal tissue.
• To identify potential biomarkers for optimizing the timing of cancer therapy.
• To address the gap in knowledge regarding the best time(s) for treating individual cancer patients.

Main Methods:

• RNA sequencing (RNA-seq) was performed on oral mucosal samples from 11 healthy volunteers at 6 time points over 24 hours.
• A cosine-based method was used to estimate individual and average peak gene expression times and amplitudes.
• Correlations between gene expression peak times and age were analyzed, adjusting for sleep timing.

Main Results:

• Several genes involved in circadian regulation (PER3, CIART, TEF, PER1, PER2, CRY2, ARNTL) and cell cycle regulation (WEE1) showed significant diurnal variation.
• Average peak expression times varied by gene, with some showing substantial individual differences (e.g., WEE1).
• Older individuals exhibited later peak expression times for PER1 and PER3.

Conclusions:

• Oral mucosal gene expression exhibits diurnal variations relevant to cancer treatment response.
• Identified genes (PER3, CIART, TEF, PER1, PER2, CRY2, ARNTL, WEE1) are potential candidates for developing biomarkers.
• These biomarkers could enable non-invasive optimization of individual cancer therapy timing.