Evaluating markers of epithelial-mesenchymal transition to identify cancer patients at risk for metastatic disease.

Autor: Busch EL; Department of Epidemiology, University of North Carolina at Chapel Hill, McGavran-Greenberg Hall, CB #7435, Chapel Hill, NC, 27599, USA.; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Keku TO; Department of Medicine, University of North Carolina at Chapel Hill, 4157 Bioinformatics Building, CB #7555, Chapel Hill, NC, 27599, USA., Richardson DB; Department of Epidemiology, University of North Carolina at Chapel Hill, McGavran-Greenberg Hall, CB #7435, Chapel Hill, NC, 27599, USA., Cohen SM; Translational Pathology Laboratory, University of North Carolina at Chapel Hill, 919 Brinkhous-Bullitt, CB #7525, Chapel Hill, NC, 27599, USA., Eberhard DA; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, 450 West Drive, CB #7295, Chapel Hill, NC, 27599, USA., Avery CL; Department of Epidemiology, University of North Carolina at Chapel Hill, McGavran-Greenberg Hall, CB #7435, Chapel Hill, NC, 27599, USA., Sandler RS; Department of Epidemiology, University of North Carolina at Chapel Hill, McGavran-Greenberg Hall, CB #7435, Chapel Hill, NC, 27599, USA. rsandler@med.unc.edu.; Department of Medicine, University of North Carolina at Chapel Hill, 4157 Bioinformatics Building, CB #7555, Chapel Hill, NC, 27599, USA. rsandler@med.unc.edu.
Jazyk: angličtina
Zdroj: Clinical & experimental metastasis [Clin Exp Metastasis] 2016 Jan; Vol. 33 (1), pp. 53-62. Date of Electronic Publication: 2015 Oct 27.
DOI: 10.1007/s10585-015-9757-7
Abstrakt: Most cancer deaths are due to metastases. Markers of epithelial-mesenchymal transition (EMT) measured in primary tumor cancer cells could be helpful to assess patient risk of metastatic disease, even among those otherwise diagnosed with local disease. Previous studies of EMT markers and patient outcomes used inconsistent methods and did not compare the clinical impact of different expression cut points for the same marker. Using digital image analysis, we measured the EMT markers Snail and E-cadherin in primary tumor specimens from 190 subjects in tissue microarrays from a population-based prospective cohort of colorectal cancer patients and estimated their associations with time-to-death. After measuring continuous marker expression data, we performed a systematic search for the cut point for each marker with the best model fit between dichotomous marker expression and time-to-death. We also assessed the potential clinical impact of different cut points for the same marker. After dichotomizing expression status at the statistically-optimal cut point, we found that Snail expression was not associated with time-to-death. When measured as a weighted average of tumor cores, low E-cadherin expression was associated with a greater risk of dying within 5 years of surgery than high expression (risk difference = 33 %, 95 % confidence interval 3-62 %). Identifying a clinically-optimal cut point for an EMT marker requires trade-offs between strength and precision of the association with patient outcomes, as well as consideration of the number of patients whose treatments might change based on using the marker at a given cut point.
Databáze: MEDLINE
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