Deregulated expression of circadian clock genes in gastric cancer.
BACKGROUND
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. 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.


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.


RESULTS
We 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).


CONCLUSIONS
Our results suggest deregulated expressions of circadian clock genes exist in GC and circadian rhythm disturbance may be associated with the development of GC.
Ming-Luen
ML
Hu
Kun-Tu
KT
Yeh
Pai-Mei
PM
Lin
Cheng-Ming
CM
Hsu
Hui-Hua
HH
Hsiao
Yi-Chang
YC
Liu
Hugo You-Hsien
HY
Lin
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road,Kwei-Shan 333 Tao-Yuan, Taiwan. shlin@cc.kmu.edu.tw.
Sheng-Fung
SF
Lin
Ming-Yu
MY
Yang
D056930:ARNTL Transcription Factors / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D056926:CLOCK Proteins / Q000235:genetics*; D016022:Case-Control Studies; D056931:Cryptochromes / Q000235:genetics*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D056950:Period Circadian Proteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D056931:Cryptochromes; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D056950:Period Circadian Proteins; D056926:CLOCK Proteins