Identification of the possible therapeutic targets in the insulin-like growth factor 1 receptor pathway in a cohort of Egyptian hepatocellular carcinoma complicating chronic hepatitis C type 4

  • Nada M.K. Mabrouk Department of Pathology, University of Alexandria, Alexandria - Egypt https://orcid.org/0000-0002-2849-9961
  • Dalal M. Elkaffash Alexandria Regional Center for Women's Health and Development, Alexandria and Department of Clinical and Chemical Pathology, University of Alexandria, Alexandria - Egypt https://orcid.org/0000-0002-7919-8958
  • Mona Abdel-Hadi Department of Pathology, University of Alexandria, Alexandria - Egypt https://orcid.org/0000-0002-3655-4529
  • Salah-ElDin Abdelmoneim Department of Clinical Oncology and Nuclear Medicine, University of Alexandria, Alexandria - Egypt https://orcid.org/0000-0002-4373-5168
  • Sameh Saad ElDeen Department of Clinical and Chemical Pathology, University of Alexandria, Alexandria - Egypt https://orcid.org/0000-0002-1666-0738
  • Gihan Gewaifel Public Health Department, Faculty of Medicine, Alexandria University, Alexandria - Egypt
  • Khaled A. Elella Department of General Surgery, University of Alexandria, Alexandria - Egypt
  • Maher Osman Department of General Surgery, University of Alexandria, Alexandria - Egypt
  • Nahed Baddour Department of Pathology, University of Alexandria, Alexandria - Egypt https://orcid.org/0000-0003-1325-2832
Keywords: Gene expression, Hepatitis C virus, Hepatocellular carcinoma, Molecular therapeutic targets

Abstract

Background: Molecular targeted drugs are the first line of treatment of advanced hepatocellular carcinoma (HCC) due to its chemo- and radioresistant nature. HCC has several well-documented etiologic factors that drive hepatocarcinogenesis through different molecular pathways. Currently, hepatitis C virus (HCV) is a leading cause of HCC. Therefore, we included a unified cohort of HCV genotype 4-related HCCs to study the expression levels of genes involved in the insulin-like growth factor 1 receptor (IGF1R) pathway, which is known to be involved in all aspects of cancer growth and progression.

Aim: Determine the gene expression patterns of IGF1R pathway genes in a cohort of Egyptian HCV-related HCCs. Correlate them with different patient/tumor characteristics. Determine the activity status of involved pathways.

Methods: Total ribonucleic acid (RNA) was extracted from 32 formalin-fixed paraffin-embedded tissues of human HCV-related HCCs and 6 healthy liver donors as controls. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RT2 Profiler PCR Array for Human Insulin Signaling Pathway was done to determine significantly up- and downregulated genes with identification of most frequently coregulated genes, followed by correlation of gene expression with different patient/tumor characteristics. Finally, canonical pathway analysis was performed using the Ingenuity Pathway Analysis software.

Results: Six genes – AEBP1, AKT2, C-FOS, PIK3R1, PRKCI, SHC1 – were significantly overexpressed. Thirteen genes – ADRB3, CEBPA, DUSP14, ERCC1, FRS3, IGF2, INS, IRS1, JUN, MTOR, PIK3R2, PPP1CA, RPS6KA1 – were significantly underexpressed. Several differentially expressed genes were related to different tumor/patient characteristics. Nitric oxide and reactive oxygen species production pathway was significantly activated in the present cohort, while the growth hormone signaling pathway was inactive.

Conclusions: The gene expression patterns identified in this study may serve as possible therapeutic targets in HCV-related HCCs. The most frequently coregulated genes may serve to guide combined molecular targeted therapies. The IGF1R pathway showed evidence of inactivity in the present cohort of HCV-related HCCs, so targeting this pathway in therapy may not be effective.

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Published
2020-04-08
How to Cite
MabroukN., ElkaffashD., Abdel-HadiM., AbdelmoneimS.-E., Saad ElDeenS., GewaifelG., ElellaK., OsmanM., & BaddourN. (2020). Identification of the possible therapeutic targets in the insulin-like growth factor 1 receptor pathway in a cohort of Egyptian hepatocellular carcinoma complicating chronic hepatitis C type 4. Drug Target Insights, 14(1), 1-11. https://doi.org/10.33393/dti.2020.1548
Section
Original Research Article