Artificial intelligence-driven precision medicine identifies prognostic WNT pathway alterations in AA colorectal cancer patients treated with FOLFOX
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Background
African Americans (AA) experience disproportionate burden of colorectal cancer (CRC). Dysregulation of the Wingless-related integration site (WNT) pathways contributes to tumor progression, yet their prognostic roles in FOLFOX-treated CRC among AA patients remain understudied.
Methods
We analyzed 2,562 CRC cases stratified by ancestry, age at onset, and FOLFOX treatment using Fisher’s exact, chi-square, and Kaplan–Meier analyses from AACR Project GENIE and cBioPortal databases. To enhance data integration and interpretation, we applied AI-HOPE and AI-HOPE-WNT, conversational artificial intelligence (AI) platforms designed to integrate clinical, genomic, and treatment data through natural language–driven queries.
Results
Overall survival analyses showed that early-onset CRC (EOCRC) AA patients treated with FOLFOX who had WNT pathway alterations experienced significantly better survival (p = 0.035). WNT pathway alterations were less frequent in late-onset AA patients treated with FOLFOX compared to those not treated (80% vs. 92%; p = 0.05).
Conclusions
Chemotherapy exposure may influence pathway-specific mutation frequencies across ancestry and disease stage. AI-enabled integrative analyses highlight the potential of conversational AI platforms to accelerate biomarker discovery and reveal ancestry- and treatment-specific vulnerabilities in CRC.
