Immunohistochemical and biochemical expression patterns of TTF-1, RAGE, GLUT-1 and SOX2 in HCV-associated hepatocellular carcinomas

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Aboushousha T.; Mamdouh S.; Hamdy H.; Helal N.; Khorshed F.; Safwat G.; Seleem M.

Journal: Asian Pacific Journal of Cancer Prevention

Publisher: Asian Pacific Organization for Cancer Prevention

Publication Date: 2018

Volume / Issue: Volume 19 / Issue 1

Pages: 219–227

ISSN: 15137368

DOI: 10.22034/APJCP.2018.19.1.219

Scopus: View on Scopus

PubMed: 29373917

Document Type: Article

Authors and Affiliations

Aboushousha T., Pathology Departmenty, October University of Modern Sciences and Arts, Giza, Egypt; Mamdouh S., Biochemistry Departmenty, October University of Modern Sciences and Arts, Giza, Egypt; Hamdy H., Surgical Department, Theodor Bilharz Research Institutey, October University of Modern Sciences and Arts, Giza, Egypt; Helal N., Pathology Departmenty, October University of Modern Sciences and Arts, Giza, Egypt; Khorshed F., Biochemistry Departmenty, October University of Modern Sciences and Arts, Giza, Egypt; Safwat G., Faculty of Biotechnology, October University of Modern Sciences and Arts, Giza, Egypt; Seleem M., National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt

Abstract

Objective: To investigate the expression of TTF-1, RAGE, GLUT1 and SOX2 in HCV-associated HCCs and in surrounding non-tumorous liver tissue. Material and Methods: Tissue material from partial hepatectomy cases for HCC along with corresponding serum samples and 30 control serum samples from healthy volunteers were studied. Biopsies were classified into: non-tumor hepatic tissue (36 sections); HCC (33 sections) and liver cell dysplasia (LCD) (15 sections). All cases were positive for HCV. Immunohistochemistry (IHC), gene extraction and quantitative real-time reverse-transcription assays (qRT-PCR) were applied. Results: By IHC, LCD and HCC showed significantly high percentages of positive cases with all markers. SOX2 showed significant increase with higher HCC grades, while RAGE demonstrated an inverse relation and GLUT-1 and TTF-1 lacked any correlation. In nontumorous-HCV tissue, we found significantly high TTF-1, low RAGE and negative SOX2 expression. RAGE, GLUT-1 and SOX2 show non-significant elevation positivity in high grade HCV compared to low grade lesions. TTF-1, RAGE and SOX2 exhibited low expression in cirrhosis compared to fibrosis. Biochemical studies on serum and tissue extracts revealed significant down-regulation of RAGE, GLUT-1 and SOX2 genes, as well as significant up-regulation of the TTF-1 gene in HCC cases compared to controls. All studied genes show significant correlation with HCC grade. In non-tumor tissue, only TTF-1 gene expression had a significant correlation with the fibrosis score. Conclusion: Higher expression of TTF-1, RAGE, GLUT-1 and SOX2 in HCC and dysplasia compared to non-tumor tissues indicates up-regulation of these markers as early events during the development of HCV-associated HCC.

Keywords

GLUT1; HCC; HCV; IHC; RAGE; SOX2; TTF1

Citation Information

Scopus Citations: 12

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