Markers of Epithelial-Mesenchymal Transition and Colorectal Cancer Mortality: Time-to-Event and Latent-Class Analyses Public Deposited

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  • March 19, 2019
Creator
  • Busch, Evan
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Most cancer arises in epithelial cells and most cancer deaths are due to metastases. Many cancer patients diagnosed with local disease according to lymph-node evaluation and radiologic imaging later experience disease recurrence within a few years of surgery. An additional measure of cancer cell detachment from the primary tumor taken in the primary tumor itself at the time of surgery might improve our ability to identify which patients are at risk for recurrence and therefore should have their treatments adjusted accordingly. Epithelial-mesenchymal transition (EMT) is a mechanism of cancer cell metastasis that connects epithelial cells to metastasis. It identifies candidate markers for the additional diagnostic test needed to stratify cancer patients by risk for recurrence. I measured the EMT markers E-cadherin, Integrin beta-6, and Snail in primary tumors from subjects in a population-based, case-only prospective cohort of colorectal cancer patients. Using Cox proportional hazards models, I estimated the association between each marker and time from surgery to death. I found that E-cadherin expression measured as a weighted average of tumor cores was associated with time to death. No other marker expression variable was associated with outcomes. Using latent class analysis, I estimated the sensitivity and specificity of E-cadherin expression as a weighted average of tumor cores to classify subjects as those likely to have cancer cells detaching or not detaching from the primary tumor at the time of surgery, in conjunction with lymph node evaluation and radiologic imaging. Latent class analysis permitted estimation of sensitivity and specificity under the realistic assumption that none of the tests constituted a gold-standard measure of whether cancer cells had detached from the primary tumor by the time of diagnosis. Across the various latent class models that I explored, I found a peak E-cadherin sensitivity of 59% and peak specificity of 94%. My results suggested that E-cadherin measurements in colorectal primary tumors at the time of surgery might improve the ability of clinicians to assess whether the patient is at risk for recurrence. Incorporating such measurements into standard colorectal cancer diagnostic procedures could thereby help to improve patient outcomes.
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  • In Copyright
Advisor
  • Avery, Christy
  • Keku, Temitope
  • Sandler, Robert
  • Eberhard, David
  • Richardson, David
Degree
  • Doctor of Public Health
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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