OBJECTIVES: The identification of useful markers for early diagnosis of human colon cancer is a major goal still in progress. Clusterin is a pleiotropic protein with a broad range of functions. It has recently drawn much attention because of its association with cancer promotion and metastasis. It is involved in prosurvival and apoptosis processes that are carried out by two different isoforms. Secreted clusterin isoform (sCLU) is cytoprotective and its prosurvival function is the basis of the current phase I/II clinical trials against prostate, lung, and breast cancers. We have already shown that in colorectal cancer (CRC) there is an increased expression of sCLU. In this report, we investigated whether sCLU is released in the blood and stool of colon cancer patients in order to study sCLU as a potential diagnostic molecular marker for colon cancer screening. METHODS: The quantitative expression of sCLU was determined by dot blot immunodosage in the serum and stool of CRC patients (n=63) and age-matched controls without clinical history of neoplasia, CRC, or systemic or bowel inflammatory disease (n=50). Unpaired t-tests and Mann-Whitney U-tests were used for continuous variables. The diagnostic performance of clusterin was appraised by means of receiver operating characteristic (ROC) curves. RESULTS: We found a significant increase of sCLU in the serum and stool of CRC patients (P=0.0002 and P<0.000, respectively) as compared with controls. ROC curves provided cutoff points showing a trade-off between sensitivity and specificity. With a cutoff point of 88.5 microg/ml, sCLU in blood showed a 55.6% sensitivity and 100% specificity, and with a cutoff point of 34.6 microg/g, the stool test reached 66.7% sensitivity and 84% specificity in discriminating between nonneoplastic and colorectal neoplastic lesions. Human cancer xenografts in nude mice indicated a positive correlation between increasing serum clusterin level and tumor size. CONCLUSIONS: This study highlights the potential of clusterin detection in stool to be a valuable tool to improve the effectiveness and efficiency of large-scale clinical cancer screening.
OBJECTIVES: The identification of useful markers for early diagnosis of humancolon cancer is a major goal still in progress. Clusterin is a pleiotropic protein with a broad range of functions. It has recently drawn much attention because of its association with cancer promotion and metastasis. It is involved in prosurvival and apoptosis processes that are carried out by two different isoforms. Secreted clusterin isoform (sCLU) is cytoprotective and its prosurvival function is the basis of the current phase I/II clinical trials against prostate, lung, and breast cancers. We have already shown that in colorectal cancer (CRC) there is an increased expression of sCLU. In this report, we investigated whether sCLU is released in the blood and stool of colon cancerpatients in order to study sCLU as a potential diagnostic molecular marker for colon cancer screening. METHODS: The quantitative expression of sCLU was determined by dot blot immunodosage in the serum and stool of CRCpatients (n=63) and age-matched controls without clinical history of neoplasia, CRC, or systemic or bowel inflammatory disease (n=50). Unpaired t-tests and Mann-Whitney U-tests were used for continuous variables. The diagnostic performance of clusterin was appraised by means of receiver operating characteristic (ROC) curves. RESULTS: We found a significant increase of sCLU in the serum and stool of CRCpatients (P=0.0002 and P<0.000, respectively) as compared with controls. ROC curves provided cutoff points showing a trade-off between sensitivity and specificity. With a cutoff point of 88.5 microg/ml, sCLU in blood showed a 55.6% sensitivity and 100% specificity, and with a cutoff point of 34.6 microg/g, the stool test reached 66.7% sensitivity and 84% specificity in discriminating between nonneoplastic and colorectal neoplastic lesions. Humancancer xenografts in nude mice indicated a positive correlation between increasing serum clusterin level and tumor size. CONCLUSIONS: This study highlights the potential of clusterin detection in stool to be a valuable tool to improve the effectiveness and efficiency of large-scale clinical cancer screening.
Authors: Sarah Strohkamp; Timo Gemoll; Sina Humborg; Sonja Hartwig; Stefan Lehr; Sandra Freitag-Wolf; Susanne Becker; Bo Franzén; Ralph Pries; Barbara Wollenberg; Uwe J Roblick; Hans-Peter Bruch; Tobias Keck; Gert Auer; Jens K Habermann Journal: Cell Mol Life Sci Date: 2017-08-28 Impact factor: 9.261
Authors: Joel Pekow; Urszula Dougherty; Yong Huang; Edward Gometz; Jeff Nathanson; Greg Cohen; Shawn Levy; Masha Kocherginsky; Nanda Venu; Maria Westerhoff; John Hart; Amy E Noffsinger; Stephen B Hanauer; Roger D Hurst; Alessandro Fichera; Loren J Joseph; Qiang Liu; Marc Bissonnette Journal: Inflamm Bowel Dis Date: 2013-03 Impact factor: 5.325
Authors: François Autelitano; Denis Loyaux; Sébastien Roudières; Catherine Déon; Frédérique Guette; Philippe Fabre; Qinggong Ping; Su Wang; Romane Auvergne; Vasudeo Badarinarayana; Michael Smith; Jean-Claude Guillemot; Steven A Goldman; Sridaran Natesan; Pascual Ferrara; Paul August Journal: PLoS One Date: 2014-10-31 Impact factor: 3.240
Authors: Itzhak Avital; Russell C Langan; Thomas A Summers; Scott R Steele; Scott A Waldman; Vadim Backman; Judy Yee; Aviram Nissan; Patrick Young; Craig Womeldorph; Paul Mancusco; Renee Mueller; Khristian Noto; Warren Grundfest; Anton J Bilchik; Mladjan Protic; Martin Daumer; John Eberhardt; Yan Gao Man; Björn Ldm Brücher; Alexander Stojadinovic Journal: J Cancer Date: 2013-03-01 Impact factor: 4.207