Globo H expression in metastatic colorectal cancer (CRC)

3527 Background: Globo H is a carbohydrate antigen that is highly expressed on the cell surface of epithelial cancers but not in normal tissue, and has been reported to correlate with poor prognosis. An attractive therapeutic target, Globo H-targeted agents are being tested in early clinical trials (e.g., OBI-833, a Globo H antigen conjugated to a mutated diphtheria toxin with potential antineoplastic activities, and OBI-999, an antibody-drug conjugate (ADC) consisting of a Globo H monoclonal antibody with a synthetic antineoplastic agent). We aim to describe the molecular features associated with Globo H expression in CRC. Methods: A total of 7,604 CRC tumors were tested by Caris Life Sciences (Phoenix, AZ) by NextGen DNA and RNA sequencing. The expression of β3GalT5, FUT-1 and FUT-2 were evaluated as surrogates for Globo H expression as they are the key enzymes in its biosynthesis. An average z-score of the 3 genes (GloboH) and of β3GalT5 (B3) alone were calculated; tumors with top quartile z-scores were considered expression-high (Q4) and bottom quartile, expression-low (Q1). QuantiSEQ was used to assess immune cell infiltration in the tumor microenvironment (TME). Statistical significance was determined using chi-square/Fisher-Exact and adjusted for multiple comparisons (q=10) (11.4% vs. 8.3%), PD-L1 positive (5.7% vs. 3.4%) and MSI-H/dMMR (8.3% vs. 5.5%). Strong positive associations were seen with mutations in BRAF, KRAS, RSPO3 fusion, and cMYC amplification with B3 alone and GloboH (all q