In:
Hepatology Communications, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 1 ( 2022-01), p. 194-208
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.
Type of Medium:
Online Resource
ISSN:
2471-254X
,
2471-254X
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2022
detail.hit.zdb_id:
2881134-3
