Screening remains the key intervention for colorectal cancer (CRC) control and prevention as detection and removal of premalignant lesions can prevent progression to cancer. Colonoscopy, the gold standard for CRC screening, is an invasive and costly procedure resulting in low compliance in both the general and the under- screened populations, including low-income and early-onset young patients. Feces-screening methods also suffer low compliance rates. Affordable and minimally invasive approaches are urgently warranted to address low screening rates and prevent CRC through early detection. We are proposing to explore the concept of field effect in CRC or simultaneous occurrence of subtle alterations distal from precancerous polyps in the colon, in an innovative way, to develop a new screening modality for CRC. Mast cells (MC) are innate immune cells located close to the intestinal epithelium and blood vessels at homeostasis, whose accumulation is an essential feature of intestinal polyposis in mice and of invasive intestinal lesions. We hypothesized that MC might slough off in the colonic lumen upon precancerous transformation, but not in normal healthy cases, thus being accessible by rectal swabbing, together with other cells. Combining our dual expertise in quantitative imaging and mast cell (MC) biology, we surmise that swab-collected cells might be analyzed on microscopy slides after processing and staining for MC using bright-field microscopy and image analysis software. Our preliminary results using two preclinical models of CRC, the genetic ApcMin/+ mouse model and the azoxymethane/dextran sulfate sodium-induced colitis leading to CRC, indicate the presence of swab MC in polyp carrying but not in healthy polyp-free, inflamed polyp-free, cancer-free or wild type mice. To ensure standardized sample analysis, we propose to develop a computational imaging method for swab MC detection by integrating MC-restricted morphometric descriptors. Further biological and technical validations will be performed. If confirm, our working hypothesis will be tested in a human pilot study.

Public Health Relevance

Screening is the best method to prevent colorectal cancer (CRC). Current methods remain invasive, yielding low compliance. Our preclinical studies suggest that the appearance of mast cells (MC) among cells collected through rectal swabbing may have a potential predictive/diagnostic value as swab MC correlate with the presence of pre-cancerous lesions upstream in the colon. A computerized imaging method will be developed for unbiased MC detection and a human pilot study performed after successful completion of biological and technical validation studies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA245651-01A1
Application #
10044350
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Young, Matthew R
Project Start
2020-07-01
Project End
2022-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Pathology
Type
Schools of Medicine
DUNS #
041387846
City
Columbia
State
SC
Country
United States
Zip Code
29208