RGD Reference Report - 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. - Rat Genome Database

RGD Reference Report - 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. - Rat Genome Database

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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.
Authors:	Mabrouk, Nada M K Elkaffash, Dalal M Abdel-Hadi, Mona Abdelmoneim, Salah-ElDin Saad ElDeen, Sameh Gewaifel, Gihan Elella, Khaled A Osman, Maher Baddour, Nahed
Citation:	Mabrouk NMK, etal., Drug Target Insights. 2020 Apr 8;14:1-11. doi: 10.33393/dti.2020.1548. eCollection 2020.
RGD ID:	150340613
Pubmed:	PMID:33132693 (View Abstract at PubMed)
PMCID:	PMC7597224 (View Article at PubMed Central)
DOI:	DOI:10.33393/dti.2020.1548 (Journal Full-text)
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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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
INS	Human	hepatocellular carcinoma		HEP		associated with Chronic Hepatitis C and mRNA:decreased expression:liver (human)	RGD

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Genes (Homo sapiens)

INS (insulin)

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