Globo H Is a Promising Theranostic Marker for Intrahepatic Cholangiocarcinoma.

Tsai-Hsien Hung, Jung-Tung Hung, Chiao-En Wu, Yenlin Huang, Chien-Wei Lee, Chau-Ting Yeh, Yi-Hsiu Chung, Fei-Yun Lo, Li-Chun Lai, John K Tung, John Yu, Chun-Nan Yeh, Alice L Yu

Hepatology communications 2022 Jan

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Recent studies support the development of cancer therapeutics to target Globo H-ceramide, the most prevalent tumor-associated carbohydrate anti gen in epithelial cancers. Herein, we evaluated the expression of Globo H and its prognostic significance in intrahepatic cholangiocarcinoma (ICC) and conducted preclinical studies to assess the antitumor activity of Globo H-specific antibody in thioacetamide (TAA)-induced ICC in rats. Globo H-ceramide in tumor specimens was detected by immunohistochemistry (IHC) and mass spectrometry. Antitumor efficacy of anti-Globo H mAbVK9 was evaluated in TAA-induced ICC in rat. Natural killer (NK) cells and their related genes were analyzed by IHC and quantitative real-time polymerase chain reaction. Data mining revealed that B3GALT5 and FUT2, the key enzymes for Globo H biosynthesis, were significantly up-regulated in human ICC. In addition, Globo H expression was detected in 41% (63 of 155) of ICC tumor specimens by IHC staining, and validated by mass spectrometric analysis of two IHC-positive tumors. Patients with Globo H positive tumors had significantly shorter relapse-free survival (RFS) and overall survival (P = 0.0003 and P = 0.002, respectively). Multivariable Cox regression analysis identified Globo H expression as an independent unfavorable predictor for RFS (hazard ratio: 1.66, 95% confidence interval: 1.08-2.36, P = 0.02) in ICC. Furthermore, gradual emergence of Globo H in liver tissues over 6 months in TAA-treated rats recapitulated the multistage progression of ICC in vivo. Importantly, administration of anti-Globo H mAbVK9 in rats bearing TAA-induced ICC significantly suppressed tumor growth with increased NK cells in the tumor microenvironment. Conclusion: Globo H is a theranostic marker in ICC. © 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.

Citation

Tsai-Hsien Hung, Jung-Tung Hung, Chiao-En Wu, Yenlin Huang, Chien-Wei Lee, Chau-Ting Yeh, Yi-Hsiu Chung, Fei-Yun Lo, Li-Chun Lai, John K Tung, John Yu, Chun-Nan Yeh, Alice L Yu. Globo H Is a Promising Theranostic Marker for Intrahepatic Cholangiocarcinoma. Hepatology communications. 2022 Jan;6(1):194-208