BRAF-V600E and microsatellite instability prediction through CA-19-9/CEA ratio in patients with colorectal cancer

Early identification of colorectal cancer (CRC) patients that are BRAF-V600E mutant and/or microsatellite instability-high (MSI-High), has both prognostic and predictive value. We wanted to highlight an observation of utilizing 2 simple, rapid and universally available lab tests, i.e., carbohydrate cancer antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) tumor markers, the ratio (CA-19-9/CEA) of which can distinctly identify these patients from other molecular subsets of CRC.

All patients with metastatic CRC from December 2016 to February 2019 were identified, and included in the study if they had both CA19-9 and CEA tests available. Circulating tumor DNA (ctDNA) testing and tissue genetic testing results were used to categorize patients into BRAF V600E microsatellite stable (MSS), MSI-High, RAS mutant MSS and RAS/RAF wild type CRCs. Kruskal-Wallis test was used to compare the CA19-9/CEA ratio between mutation types and the pairwise p values were adjusted for multiple comparisons with Holm method. For sensitivity analysis, the same analysis was repeated for the mean and median ratio of each patient. All tests were two-sided with alpha level set at 0.05 for statistical significance.

BRAF-V600E MSS CRC patients had a discordantly profound elevation in CA-19-9 levels as opposed to the CEA levels. Patients in the BRAF V600E MSS subset had the highest median CA19-9/CEA ratio versus the least median ratio in MSI-High patients. The median of maximum CA-19-9/CEA ratio was 28.92 (range, 2.76-707.27) in BRAF-V600E MSS patients and 4.06 (range, 0.46-166.74) in MSI-High subset of patients.

To date, this is the first report utilizing the ratio of tumor markers CA19-9/CEA as a predictive rather than just prognostic tool to identify BRAF-V600E MSS and MSI-High CRC patients.