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Author Notes:

Corresponding author: qlong@emory.edu, Phone: +01 404 712 9975, Fax: +01 404 727 1370

Subjects:

Keywords:

  • Functional biomarker
  • Functional logistic models
  • Joint modeling
  • Measurement errors
  • Semiparametric estimation
  • Sufficient score

Semiparametric Estimation for Joint Modeling of Colorectal Cancer Risk and Functional Biomarkers Measured with Errors

Tools:

Journal Title:

Biometrical Journal

Volume:

Volume 53, Number 3

Publisher:

, Pages 393-410

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Summary This research is motivated by a pilot colorectal adenoma study, where the outcome of interest is the presence of colorectal adenoma representing risk for colorectal cancer, and the predictors of interest are protein biomarkers that are repeatedly measured with errors along the length of a microscopic structure in the human colon, the colon crypt. Biomarkers of this type are referred to as functional biomarkers. The investigators are interested in identifying features of functional biomarkers that are associated with risk for colorectal cancer. In this paper, we investigate a joint modeling approach, where the binary clinical outcome is modeled using a logistic regression model with the unobserved true functional biomarkers as predictors. Most existing methods are developed either for linear models or for functional biomarkers measured without errors and cannot be directly applied to our data. The applicable methods include a two-step method and a maximum likelihood method, which have some limitations. We propose a robust semiparametric method to overcome the limitations of the existing methods. We study the properties of the proposed method, and show in simulations that it compares favorably with other methods and also offers significant savings in CPU time. We analyze the pilot colorectal adenoma data and show that expression levels of APC, a tumor suppressor gene, in the transitional area from the proliferation zone to the differentiation zone of colon crypts are likely associated with risk for colorectal cancer. Given the relatively small sample size in the pilot study, our results need to be validated in future full-scale studies.
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