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Globo H Is a Promising Theranostic Marker for Intrahepatic Cholangiocarcinoma.
- Source :
-
Hepatology communications [Hepatol Commun] 2022 Jan; Vol. 6 (1), pp. 194-208. Date of Electronic Publication: 2021 Aug 24. - Publication Year :
- 2022
-
Abstract
- Recent studies support the development of cancer therapeutics to target Globo H-ceramide, the most prevalent tumor-associated carbohydrate antigen 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.<br /> (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
- Subjects :
- Animals
Antibodies, Monoclonal therapeutic use
Antigens, Tumor-Associated, Carbohydrate immunology
Bile Duct Neoplasms drug therapy
Cholangiocarcinoma drug therapy
Disease Models, Animal
Humans
Male
Prognosis
Rats, Sprague-Dawley
Risk Factors
Rats
Antigens, Tumor-Associated, Carbohydrate analysis
Bile Duct Neoplasms metabolism
Cholangiocarcinoma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2471-254X
- Volume :
- 6
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Hepatology communications
- Publication Type :
- Academic Journal
- Accession number :
- 34558839
- Full Text :
- https://doi.org/10.1002/hep4.1800