Journal article
Circadian Gene Expression and Clinicopathologic Correlates in Pancreatic Cancer
Journal of gastrointestinal surgery, v 17(3), pp 443-449
01 Mar 2013
PMID: 23254314
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The circadian rhythm is responsible for physiologic homeostasis, behavior, and components of multiple metabolic processes. Disruption of the circadian rhythm is associated with cancer development, and several circadian clock genes have been implicated in loss of cell cycle control, impaired DNA damage repair, and subsequent tumor formation. Here, we investigated the expression profiles of several circadian clock genes in pancreatic ductal adenocarcinoma (PDA).
Quantitative real-time polymerase chain reaction was used to examine the circadian clock genes (brain-muscle-like (Bmal)-ARNTL, circadian locomotor output cycles kaput (Clock), cryptochrome 1 (Cry1), cryptochrome 2 (Cry2), casein kinase 1 epsilon (CK1 epsilon), period 1 (Per1), period 2 (Per2), period 3 (Per3), timeless (Tim), and timeless-interacting protein (Tipin)) in PDA, as well as matching adjacent and benign tissue. Logistic regression models with robust variance were used to analyze the gene expression levels, and Kaplan-Meier survival curves were generated based on gene expression.
In the tumor tissue of PDA patients, compared to their matched adjacent tissue, expression levels of all circadian genes were lower, with statistical significance for Per1, Per2, Per3, Cry1, Cry2, Tipin, Tim, CK1 epsilon, Bmal-ARNTL, and Clock (p < 0.025). PDA tumors also expressed significantly lower levels of the circadian genes when compared to benign lesions for Per1, Per2, Per3, Cry2, Tipin, and CK1 epsilon. A significant association between low levels of expression in the tumors and reduced survival was found with Per1, Per2, Per3, Cry2, Tipin, CK1 epsilon, Clock, and Bmal-ARNTL.
Our results reveal for the first time a dysregulated transcription of several circadian genes in PDA. Elevation of the gene levels in the benign and matched adjacent tissues may be indicative of their role during the process of tumorigenesis. The potential of using circadian genes as predictive markers of the outcomes and survival and distinguishing PDA from benign pancreas must be studied in larger populations to validate and demonstrate their eventual clinical utility.
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Details
- Title
- Circadian Gene Expression and Clinicopathologic Correlates in Pancreatic Cancer
- Creators
- Daniel Relles - Thomas Jefferson UniversityJocelyn Sendecki - Thomas Jefferson UniversityGalina Chipitsyna - Thomas Jefferson UniversityTerry Hyslop - Thomas Jefferson UniversityCharles J. Yeo - Thomas Jefferson UniversityHwyda A. Arafat - Thomas Jefferson University
- Publication Details
- Journal of gastrointestinal surgery, v 17(3), pp 443-449
- Publisher
- Springer Nature
- Number of pages
- 7
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:000314725500007
- Scopus ID
- 2-s2.0-84873746527
- Other Identifier
- 991022047280504721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Gastroenterology & Hepatology
- Surgery