정유진 (충남대학교)

안현주 (충남대학교)

정유진 (충남대학교)

정수민 (충남대학교)

오명진 (충남대학교)

안현주 (충남대학교)

Patient-derived cancer organoids serve as preclinical models by preserving the genetic and  histological characteristics of primary tumors. However, whether these models faithfully recapitulate tumor-associated glycosylation features—particularly aberrant sialylation, which plays a key role in cancer immune evasion via Siglec receptor interactions—remains poorly understood due to the lack of systematic quantitative evaluation. Here, we employed a mass spectrometry-based platform to evaluate the sialylation fidelity of colorectal cancer (CRC) organoids. Nano LC/Q-TOF-MS N-glycan profiling (n = 3) revealed a 19.5% relative reduction in sialylated glycans in CRC versus normal organoids. This trend contrasts with the hypersialylation commonly reported in primary CRC tissues, underscoring the need for direct comparison with patient tumor samples to validate organoid fidelity. To achieve sialic acid epitope quantitation, we applied a label-free UHPLC-MS/MS MRM method for the absolute quantification of Neu5Ac and Neu5Gc. This targeted assay demonstrated significant differences in Neu5Ac levels between normal and CRC organoids. Neu5Gc, a non-human immunogenic sialic acid, was detected in both models, suggesting potential incorporation from culture materials. These findings underscore the need for quantitative sialylation profiling, including future comparison with primary tumor tissue, to ensure immunological fidelity in preclinical screening of sialic acid-targeted immunotherapies.