Novel Circulating Tumor Cell Assay for Detection of Colorectal Adenomas and Cancer

Abstract

OBJECTIVES:There is a significant unmet need for a blood test with adequate sensitivity to detect colorectal cancer (CRC) and adenomas. We describe a novel circulating tumor cell (CTC) platform to capture colorectal epithelial cells associated with CRC and adenomas.METHODS:Blood was collected from 667 Taiwanese adults from 2012 to 2018 before a colonoscopy. The study population included healthy control subjects, patients with adenomas, and those with stage I–IV CRC. CTCs were isolated from the blood using the CellMax platform. The isolated cells were enumerated, and an algorithm was used to determine the likelihood of detecting adenoma or CRC. Nominal and ordinal logistic regression demonstrated that CTC counts could identify adenomas and CRC, including CRC stage.RESULTS:The CellMax test demonstrated a significant association between CTC counts and worsening disease status (Cuzick's P value < 0.0001) with respect to the adenoma-carcinoma sequence. The test showed high specificity (86%) and sensitivity across all CRC stages (95%) and adenomatous lesions (79%). The area under the curve was 0.940 and 0.868 for the detection of CRC and adenomas, respectively.DISCUSSION:The blood-based CTC platform demonstrated high sensitivity in detecting adenomas and CRC, as well as reasonable specificity in an enriched symptomatic patient population.TRANSLATIONAL IMPACT:If these results are reproduced in an average risk population, this test has the potential to prevent CRC by improving patient compliance and detecting precancerous adenomas, eventually reducing CRC mortality.

Colorectal Adenomas—Genetics and Searching for New Molecular Screening Biomarkers

“…Considering the low occurrence of CTCs in the bloodstream during CRC metastatic process, the utilization of CTCs for a screening of CRC early stages or precancerous lesions represents a very ambitious aim. The recent study of Tsai et al [134] has accepted this challenging topic. On the day of the colonoscopy, 8 ml of peripheral blood was collected from 667 Taiwanese subjects (in detail the study consisted of 235 healthy controls, 107 subjects with adenomatous polyps, and 325 patients with CRC across all stages I-IV).…”

Effects of Insulin Pathway on Glucose and Lipid Metabolism Disorder in Different Pathological Types of Colorectal Adenomas

“…However, we cannot ignore the potential harm causing by advanced adenomas, and the existing data are not complete enough for patients to stop all further treatment after the adenoma is removed. 16 Our findings showed that disorders of glucose and lipid metabolism affect the progression of advanced adenomas, so the analysis of colorectal adenomas becomes extremely important.…”

Circulating Tumor Cells from Enumeration to Analysis: Current Challenges and Future Opportunities

“…The isolation and capture of CTCs based on biological characteristics of those heterogeneous cells utilize different biological markers expressed in the cells ( Table 2 ) [ 18 , 19 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 45 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. The first data describing the detection and characterization of carcinoma cells in the systemic circulation (bone marrow) based on cytokeratin and MUC-1 glycoprotein expression in epithelial cancer cells, but not in healthy cells, were published 25 years ago [ 63 ].…”