Abstract

BackgroundGastric cancer (GC), an aggressive malignant tumor of the alimentary tract, is a leading cause of cancer-related death. Circadian rhythm exhibits a 24-hour variation in physiological processes and behavior, such as hormone levels, metabolism, gene expression, sleep and wakefulness, and appetite. Disruption of circadian rhythm has been associated with various cancers, including chronic myeloid leukemia, head and neck squamous cell carcinoma, hepatocellular carcinoma, endometrial carcinoma, and breast cancer. However, the expression of circadian clock genes in GC remains unexplored.MethodsIn this study, the expression profiles of eight circadian clock genes (PER1, PER2, PER3, CRY1, CRY2, CKIϵ, CLOCK, and BMAL1) of cancerous and noncancerous tissues from 29 GC patients were investigated using real-time quantitative reverse-transcriptase polymerase chain reaction and validated through immunohistochemical analysis.ResultsWe found that PER2 was significantly up-regulated in cancer tissues (p < 0.005). Up-regulated CRY1 expression was significantly correlated with more advanced stages (stage III and IV) (p < 0.05).ConclusionsOur results suggest deregulated expressions of circadian clock genes exist in GC and circadian rhythm disturbance may be associated with the development of GC.

Highlights

  • Gastric cancer (GC), an aggressive malignant tumor of the alimentary tract, is a leading cause of cancer-related death

  • Disease severity and circadian clock gene expression in GC patients We divided the patients into earlier stages and more advanced stages for correlation analysis with circadian clock gene expression and found that CRY1 expression was upregulated in more advanced cancer stages (p < 0.05) (Figure 3A)

  • Age and circadian clock gene expression in GC patients To rule out the possibility that the altered circadian clock gene expression was due to age differences, we divided the patients into two groups (< 60 years-old and > 60 years-old) for correlation analysis with circadian clock gene expression

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Summary

Introduction

Gastric cancer (GC), an aggressive malignant tumor of the alimentary tract, is a leading cause of cancer-related death. Circadian rhythm exhibits a 24-hour variation in physiological processes and behavior, such as hormone levels, metabolism, gene expression, sleep and wakefulness, and appetite. The expression of circadian clock genes in GC remains unexplored. Methods: In this study, the expression profiles of eight circadian clock genes (PER1, PER2, PER3, CRY1, CRY2, CKIε, CLOCK, and BMAL1) of cancerous and noncancerous tissues from 29 GC patients were investigated using real-time quantitative reverse-transcriptase polymerase chain reaction and validated through immunohistochemical analysis. Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide [1,2]. Detection of GC often offers a better prognosis but most patients are diagnosed with GCs at late stages.

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