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Disruption of clock gene expression in human colorectal liver metastases.

ABSTRACT: The circadian timing system controls about 40 % of the transcriptome and is important in the regulation of a wide variety of biological processes including metabolic and proliferative functions. Disruption of the circadian clock could have significant effect on human health and has an important role in the development of cancer. Here, we compared the expression levels of core clock genes in primary colorectal cancer (CRC), colorectal liver metastases (CRLM), and liver tissue within the same patient. Surgical specimens of 15 untreated patients with primary CRC and metachronous CRLM were studied. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of 10 clock genes: CLOCK, BMAL1, PER1, PER2, PER3, CRY1, CRY2, CSNK1E, TIM, TIPIN, and 2 clock-controlled genes: Cyclin-D1, and WEE1. Expression levels of 7 core clock genes were downregulated in CRLM: CLOCK (p?=?0.006), BMAL1 (p?=?0.003), PER1 (p?=?0.003), PER2 (p?=?0.002), PER3 (p?

SUBMITTER: Huisman SA

PROVIDER: S-EPMC5097083 | biostudies-other | 2016 Oct

REPOSITORIES: biostudies-other

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Disruption of clock gene expression in human colorectal liver metastases.

Huisman Sander A SA Ahmadi Ali R AR IJzermans Jan N M JN Verhoef Cees C van der Horst Gijsbertus T J GT de Bruin Ron W F RW

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 20160804 10

The circadian timing system controls about 40 % of the transcriptome and is important in the regulation of a wide variety of biological processes including metabolic and proliferative functions. Disruption of the circadian clock could have significant effect on human health and has an important role in the development of cancer. Here, we compared the expression levels of core clock genes in primary colorectal cancer (CRC), colorectal liver metastases (CRLM), and liver tissue within the same pati ...[more]

PMID: 27492458

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Project description:UnlabelledIntegrins are cell surface adhesion molecules (CAM) that regulate via intercellular and cell-matrix signaling various cellular processes including wound healing, cell differentiation, division, growth, migration and metastatic dissemination. Although a correlation between carcinogenesis and changes in integrin expression, especially ?1 integrin, has been reported, its role in colorectal liver metastases remains unclear. This study aimed to evaluate the expression of ?1 integrin in colorectal liver metastases and to correlate the pattern of expression with clinicopathological features and to investigate the putative role of ?1 integrin expression on survival of these patients.MethodsFormalin-fixed, paraffin-embedded (FFPE) tumor samples of 81 patients who were operated because of colorectal liver metastases without any neoadjuvant therapy were obtained and stained with hematoxylin and eosin (H & E). An immunohistochemical examination was performed using Dako, Peroxidase/DAB kit and a primary monoclonal ?1 integrin (CD29, fibronectin receptor subunit beta; ab3167, Abcam plc). ?1 integrin expression was evaluated according to the immunoreactive score of Remmele and Stegner and was related with clinicopathological features of prognostic significance and with disease-free and overall survival as well. Statistical analysis was performed using SPSS version 21.0.Results?1 integrin was overexpressed in tumor cells in 37 (48%) patients and in stromal cell in 27 (33%) patients. The ?1 expression was not statistically correlated with clinicopathological features of the primary tumors but it was statistically correlated (p=0.03) with the histological grading of liver metastases. Kaplan-Meier survival analysis showed that there is a tendency but no statistically significant correlation in disease-free and overall survival.ConclusionConsidering that expression of ?1 integrin in colorectal liver metastases remains controversial, specially its relation with survival of patients, we showed that the ?1 expression represents a reliable prognostic factor regarding the grading of liver metastases of CRC and our findings imply that ?1 integrin expression profiles may have further potential in identifying the stage of colorectal liver metastases and being a marker of prognosis in these patients.

Dataset Information

Disruption of clock gene expression in human colorectal liver metastases.

Publications

Disruption of clock gene expression in human colorectal liver metastases.

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