Dataset Information

Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance.

ABSTRACT:

Background

Colorectal cancer (CRC) represents the third leading cause of cancer-related death in the United States. Lack of reliable biomarkers remains a critical issue for early detection of CRC. In this study, we investigated the potential predictive values of circulating prostaglandin (PG) biosynthesis in CRC risk.

Methods

Profiles of circulating PG biosynthesis and platelet counts were determined in healthy subjects (n = 16), familial adenomatous polyposis (FAP) patients who were classified as regular aspirin users (n = 14) or nonusers (n = 24), and CRC patients with (n = 18) or without FAP history (n = 20). Immunohistochemistry staining was performed on biopsy samples.

Results

Analysis of circulating PG biosynthesis unexpectedly revealed that CRC progression is accompanied by a pronounced elevation of circulating thromboxane A2 (TXA₂) levels. When a circulating TXA₂ level of 1000 pg/mL was selected as a practical cutoff point, 95% of CRC patients were successfully identified. Further study suggested that the TXA₂ pathway is constitutively activated during colorectal tumorigenesis and required for anchorage-independent growth of colon cancer cells.

Conclusions

This study established the importance of the TXA₂ pathway in CRC pathophysiology, and laid the groundwork for introducing a TXA₂-targeting strategy to CRC prevention, early detection and management.

SUBMITTER: Li H

PROVIDER: S-EPMC4347518 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Publications

Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance.

Li Haitao H Liu Kangdong K Boardman Lisa A LA Zhao Yuzhou Y Wang Lei L Sheng Yuqiao Y Oi Naomi N Limburg Paul J PJ Bode Ann M AM Dong Zigang Z

EBioMedicine 20150201 2

<h4>Background</h4>Colorectal cancer (CRC) represents the third leading cause of cancer-related death in the United States. Lack of reliable biomarkers remains a critical issue for early detection of CRC. In this study, we investigated the potential predictive values of circulating prostaglandin (PG) biosynthesis in CRC risk.<h4>Methods</h4>Profiles of circulating PG biosynthesis and platelet counts were determined in healthy subjects (n = 16), familial adenomatous polyposis (FAP) patients who w ...[more]

PMID: 25750933

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Project description:Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC). Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells especially in patients with distant metastasis was a prerequisite to select candidate genes. The mRNA expression of candidate gene was investigated by quantitative reversetranscription polymerase chain reaction (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study, and investigated the relationship between the expression and the clinicopathological feature in 274 CRC patients. Results: We identified 6 genes as candidates related to distant metastasis in CRC patients by microarray analysis. Among these genes, Osteoprotegerin (OPG) is known to have an association with aggressiveness in several cancers through inhibiting apoptosis by neutralizing the function of tumor necrosis factor related apoptosis inducing ligand (TRAIL). The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastasis than those without metastasis. The overexpression of OPG protein was significantly associated with worse overall survival and relapse free survival (RFS). Moreover, the overexpression of OPG protein was an independent risk factor for recurrence of CRC. Conclusion: The overexpression of OPG would be a predictive biomarker of recurrence and a target of the treatment for CRC. Total of 148 microarray datasets obtained from LCM and homogenized tissues of colorectal cancer patients were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software with affy package from BioConductor. Normalization was separately performed for LCM dataset and homogenized tissue dataset. The normalized gene expression levels were presented as log2-transformed values by RMA.

Project description:During the process of metastasis, which is the leading cause of cancer-related death, cancer cells dissociate from primary tumors, migrate to distal sites, and finally colonize, eventually leading to the formation of metastatic tumors. The migrating tumor cells in circulation, e.g., those found in peripheral blood (PB) or bone marrow (BM), are called circulating tumor cells (CTCs). CTCs in the BM are generally called disseminated tumor cells (DTCs). Many studies have reported the detection and characterization of CTCs to facilitate early diagnosis of relapse or metastasis and improve early detection and appropriate treatment decisions. Initially, epithelial markers, such as EpCAM and cytokeratins (CKs), identified using immunocytochemistry or reverse transcription polymerase chain reaction (RT-PCR) were used to identify CTCs in PB or BM. Recently, however, other markers such as human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and immuno-checkpoint genes also have been examined to facilitate detection of CTCs with metastatic potential. Moreover, the epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs) have also received increasing attention as important CTC markers owing to their roles in the biological progression of metastasis. In addition to these markers, researchers have attempted to develop detection or capture techniques for CTCs. Notably, however, the establishment of metastasis requires cancer-host interactions. Markers from host cells, such as macrophages, mesenchymal stem cells, and bone marrow-derived cells, which constitute the premetastatic niche, may become novel biomarkers for predicting relapse or metastasis or monitoring the effects of treatment. Biological studies of CTCs are still emerging. However, recent technical innovations, such as next-generation sequencing, are being used more commonly and could help to clarify the mechanism of metastasis. Additionally, biological findings are gradually being accumulated, adding to our body of knowledge on CTCs. In this review, we will summarize recent approaches to detect or capture CTCs. Moreover, we will introduce recent studies of the clinical and biological importance of CTCs and host cells.

Dataset Information

Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance.

Background

Methods

Results

Conclusions

Publications

Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance.

Similar Datasets

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