Galectin-3 expression is prognostic in diffuse type gastric adenocarcinoma, confers aggressive phenotype, and can be targeted by YAP1/BET inhibitors

Autor: Bin Liu, Wayne L. Hofstetter, Brian Weston, Min Xie, Ailing W. Scott, Jeannelyn S. Estrella, Sheng Ding, Jeffrey H. Lee, Akihiro Suzuki, Jaffer A. Ajani, Manoop S. Bhutani, Jiankang Jin, Lang Ma, Hironori Shiozaki, Hisashi Onodera, Randy L. Johnson, Shumei Song, Kazuki Sudo, Koyu Suzuki, Qiongrong Chen, Robert S. Bresalier, Brian D. Badgwell, Arlene M. Correa
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Galectin 3
0302 clinical medicine
Galectin-3
YAP1
Regulation of gene expression
therapeutic target
food and beverages
hemic and immune systems
Azepines
Blood Proteins
Prognosis
Phenotype
Up-Regulation
Gene Expression Regulation
Neoplastic
c-MYC
030220 oncology & carcinogenesis
Female
medicine.medical_specialty
Cell Survival
Galectins
chemical and pharmacologic phenomena
Proto-Oncogene Proteins c-myc
03 medical and health sciences
Downregulation and upregulation
Stomach Neoplasms
Cell Line
Tumor
Internal medicine
Biomarkers
Tumor
medicine
Humans
Adaptor Proteins
Signal Transducing
Cell Proliferation
Cell growth
business.industry
fungi
YAP-Signaling Proteins
Triazoles
Phosphoproteins
digestive system diseases
030104 developmental biology
Ral GTP-Binding Proteins
Cell culture
Cancer research
ral GTP-Binding Proteins
gastric adenocarcinoma
Neoplasm Grading
Translational Therapeutics
business
prognostic marker
Transcription Factors
Zdroj: British Journal of Cancer
ISSN: 1532-1827
0007-0920
Popis: Background: Overexpression of Galectin-3 (Gal-3), a β-galactoside binding protein, has been noted in many tumour types but its functional significance and clinical utility in gastric adenocarcinoma (GAC) are not well known. Methods: We studied 184 GAC patients characterised by histologic grade, sub-phenotypes (diffuse vs intestinal), and ethnicity (Asians vs North Americans). Immunohistochemistry was performed to assess the expression of Gal-3 in human GACs and we correlated it to the clinical outcomes. Cell proliferation, invasion, co-immunoprecipitation and kinase activity assays were done in genetically stable Gal-3 overexpressing GC cell lines and the parental counterparts to delineate the mechanisms of action and activity of inhibitors. Results: Most patients were men, Asian, and had a poorly differentiated GAC. Gal-3 was over-expressed in poorly differentiated (P=0.002) tumours and also in diffuse sub-phenotype (P=0.02). Gal-3 overexpression was associated with shorter overall survival (OS; P=0.026) in all patients. Although, Gal-3 over-expression was not prognostic in the Asian cohort (P=0.337), it was highly prognostic in the North American cohort (P=0.001). In a multivariate analysis, Gal-3 (P=0.001) and N-stage (P=
Databáze: OpenAIRE
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