Statistical strategies to improve the efficiency of molecular studies of colorectal cancer prognosis

P. Qu, H. Chu, J. G. Ibrahim, J. Peacock, X. J. Shen, J. Tepper, R. S. Sandler, T. O. Keku

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The evaluation of tumour molecular markers may be beneficial in prognosis and predictive in therapy. We develop a stopping rule approach to assist in the efficient utilisation of resources and samples involved in such evaluations. This approach has application in determining whether a specific molecular marker has sufficient variability to yield meaningful results after the evaluation of molecular markers in the first n patients in a study of sample size N (n≤N). We evaluated colorectal tumours for mutations (microsatellite instability, K-ras, B-raf, PI3 kinase, and TGFβR-II) by PCR and protein markers (Bcl2, cyclin D1, E-cadherin, hMLH1, ki67, MDM2, and P53) by immunohistochemistry. Using this method, we identified and abandoned potentially uninformative molecular markers in favour of more promising candidates. This approach conserves tissue resources, time, and money, and may be applicable to other studies.

Original languageEnglish (US)
Pages (from-to)2001-2005
Number of pages5
JournalBritish Journal of Cancer
Volume99
Issue number12
DOIs
StatePublished - Dec 16 2008

Bibliographical note

Funding Information:
This research was supported, in part, by grants from the National Institutes of Health (U01 CA93326 and P50 CA106991).

Funding Information:
We are conducting a population-based study of colorectal cancer in 33 county areas of North Carolina. This study, Cancer Care Outcomes and Surveillance (CanCORS), is a multicentre population-based study, funded by the National Cancer Institute, to evaluate patient, physician. and treatment factors that influence colorectal cancer outcomes. As part of the CanCORS study at the University of North Carolina, we collected tumour tissue on consenting subjects, and constructed tissue microarrays (Kononen et al, 1998) to be used for immunohistochemistry and mutational analysis as part of the UNC GI Specialized Programme in Research Excellence (SPORE) grant. We enrolled 1000 patients (N = 1000) into the study, and the study was approved by the Institutional review board (IRB) of the UNC School of Medicine. From more than 100 patients, we evaluated genetic mutations in p53 (Angelopoulou and Diamandis, 1998; Curtin et al, 2004), K-ras,

Keywords

  • Efficiency
  • Molecular markers
  • Stopping rule
  • Survival
  • Variability

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