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

Pashtoon Murtaza Kasi, Saivaishnavi Kamatham, Faisal Shahjehan, Zhuo Li, Patrick W. Johnson, Amit Merchea, Dorin T. Colibaseanu


Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.

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