Existing guidelines recommend colorectal cancer (CRC) screening for all patients over age 50. However, CRC remains the second leading cause of cancer death among Americans largely because colonoscopic screening of all the >100 million Americans over age 50 is unfeasible for both patient-related (non-compliance) and societal (inadequate endoscopic capacity and funding) reasons. Furthermore, the current practice of colonoscopy on the 3average risk4 population is remarkably inefficient2only ~6% of the screening population has significant neoplasia (advanced adenomas). Thus, a simple, non-invasive risk-stratification technique is critical to better target patients for colonoscopy. Stool analysis would be an ideal test that would engender the best patients6 compliance, although current stool tests assessing tumor cells or blood loss have dismal sensitivity. We propose a novel, more robust approach that utilizes mucus layer fecal colonocytes which are abraded from the epithelium and thus represent field carcinogenesis (the genetic/environmental fingerprint of neoplastic risk). Based on our preliminary data (156 patients), we hypothesize that the analysis of two complementary facets, nanostructural and molecular (microRNA) alterations, in mucus layer fecal colonocytes will serve as a highly accurate means of identifying field carcinogenesis and thereby serve as a non-invasive CRC screening test. Our approach is based on the combination of a novel biophotonics technology, partial wave spectroscopic microscopy (PWS), that is uniquely capable of imaging and quantification of the statistics of cell nanoscale organization and a new method to get high quality non-apoptotic fecal colonocytes in a practical fashion. In preclinical and clinical models, the performance characteristics of PWS and microRNA were outstanding, thus providing promise for a screening test. There are several requisite steps prior to the future definitive clinical validation. We will develop high-throughput PWS technology and identify the cellular location of the nanoarchitectural alterations. We will formulate and prospectively test a prediction rule that combines both nanostructural and molecular alterations. This project will confirm that nanostructural/ molecular stool analysis may provide sensitive, non-invasive risk-stratification tool, thereby heralding the era of personalized medicine for CRC population screening.

Public Health Relevance

No existing technique allows accurate and cost-effective colon cancer screening in population. This project will lead toward development of a minimally invasive optical technology that would enable colon cancer screening in general population by a simple stool analysis.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01CA165309-03
Application #
8730099
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Zhu, Claire
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201
Stypula-Cyrus, Yolanda; Mutyal, Nikhil N; Dela Cruz, Mart et al. (2014) End-binding protein 1 (EB1) up-regulation is an early event in colorectal carcinogenesis. FEBS Lett 588:829-35
Cruz, Mart Dela; Wali, Ramesh K; Bianchi, Laura K et al. (2014) Colonic mucosal fatty acid synthase as an early biomarker for colorectal neoplasia: modulation by obesity and gender. Cancer Epidemiol Biomarkers Prev 23:2413-21
Damania, Dhwanil; Subramanian, Hariharan; Backman, Vadim et al. (2014) Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer. J Biomed Opt 19:16016
Wali, Ramesh K; Hensing, Thomas A; Ray, Daniel W et al. (2014) Buccal microRNA dysregulation in lung field carcinogenesis: gender-specific implications. Int J Oncol 45:1209-15
Yi, Ji; Radosevich, Andrew J; Stypula-Cyrus, Yolanda et al. (2014) Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography. J Biomed Opt 19:36013
Cherkezyan, Lusik; Stypula-Cyrus, Yolanda; Subramanian, Hariharan et al. (2014) Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study. BMC Cancer 14:189
Roy, Hemant K; Damania, Dhwanil P; DelaCruz, Mart et al. (2013) Nano-architectural alterations in mucus layer fecal colonocytes in field carcinogenesis: potential for screening. Cancer Prev Res (Phila) 6:1111-9
Calderwood, Audrey H; Roy, Hemant K (2013) Increasing colorectal cancer screening adherence: comment on "A randomized comparison of print and web communication on colorectal cancer screening". JAMA Intern Med 173:129-31
Backman, Vadim; Roy, Hemant K (2013) Advances in biophotonics detection of field carcinogenesis for colon cancer risk stratification. J Cancer 4:251-61
Chandler, John E; Subramanian, Hariharan; Maneval, Charles D et al. (2013) High-speed spectral nanocytology for early cancer screening. J Biomed Opt 18:117002

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