Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance
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) biosy...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-02-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396414000504 |
| _version_ | 1818308960040517632 |
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| author | Haitao Li Kangdong Liu Lisa A. Boardman Yuzhou Zhao Lei Wang Yuqiao Sheng Naomi Oi Paul J. Limburg Ann M. Bode Zigang Dong |
| author_facet | Haitao Li Kangdong Liu Lisa A. Boardman Yuzhou Zhao Lei Wang Yuqiao Sheng Naomi Oi Paul J. Limburg Ann M. Bode Zigang Dong |
| author_sort | Haitao Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T07:22:34Z |
| format | Article |
| id | doaj.art-6e73a4e95a3c412c95c8e73e31255984 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-13T07:22:34Z |
| publishDate | 2015-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-6e73a4e95a3c412c95c8e73e312559842022-12-21T23:55:24ZengElsevierEBioMedicine2352-39642015-02-012216517110.1016/j.ebiom.2014.12.004Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical SignificanceHaitao Li0Kangdong Liu1Lisa A. Boardman2Yuzhou Zhao3Lei Wang4Yuqiao Sheng5Naomi Oi6Paul J. Limburg7Ann M. Bode8Zigang Dong9The Hormel Institute, University of Minnesota, Austin, MN, USAThe China–US (Henan) Hormel Cancer Institute, Zhengzhou, Henan, ChinaDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USAThe Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, ChinaThe Hormel Institute, University of Minnesota, Austin, MN, USAThe Hormel Institute, University of Minnesota, Austin, MN, USAThe Hormel Institute, University of Minnesota, Austin, MN, USADepartment of Medicine, Mayo Clinic, Rochester, MN, USAThe Hormel Institute, University of Minnesota, Austin, MN, USAThe Hormel Institute, University of Minnesota, Austin, MN, USABackground: 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.http://www.sciencedirect.com/science/article/pii/S2352396414000504Colorectal cancerFamilial adenomatous polyposisThromboxane A2 |
| spellingShingle | Haitao Li Kangdong Liu Lisa A. Boardman Yuzhou Zhao Lei Wang Yuqiao Sheng Naomi Oi Paul J. Limburg Ann M. Bode Zigang Dong Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance EBioMedicine Colorectal cancer Familial adenomatous polyposis Thromboxane A2 |
| title | Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance |
| title_full | Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance |
| title_fullStr | Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance |
| title_full_unstemmed | Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance |
| title_short | Circulating Prostaglandin Biosynthesis in Colorectal Cancer and Potential Clinical Significance |
| title_sort | circulating prostaglandin biosynthesis in colorectal cancer and potential clinical significance |
| topic | Colorectal cancer Familial adenomatous polyposis Thromboxane A2 |
| url | http://www.sciencedirect.com/science/article/pii/S2352396414000504 |
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