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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.

Colorectal carcinoma (CRC) is one of the most common cancers in the world. Preoperative radiation with concurrent chemotherapy and subsequent surgery is the standard treatment for locally advanced rectal cancer. However, the tumor response to preoperative chemoradiotherapy (pCRT) varies significantly. CSCs have been found in many human malignant tumors including rectal cancer. Several markers for CSCs have been proposed in CRC, OCT-4 and CD133 have been the most frequently researched. This study was targeted to evaluate the immunohistochemical expression of stem cell markers OCT-4 & CD133 in rectosigmoid adenocarcinomas and correlate their expressions with the grade, stage, and response of the tumor to CRT. The present study comprised 30 specimens of rectosigmoid adenocarcinoma. The primary antibodies used were: OCT-4 antibody, clone PA5-27438, and CD133 antibody, clone144305. Positive OCT-4 expression was observed in 12/30 cases. A significant relationship was found between OCT-4 expression and tumor stage and sex of the patients. No statistically significant relation was found between OCT-4 expression and age of the patients, tumor grade, lymph node stage, pathological response to CRT, OS, or the expression of CD133. 20/30 cases were positively stained for CD133, no significant correlation between CD133 expression and any of the clinicopathological parameters. OCT-4 was expressed in 40% and CD133 in 66% of rectosigmoid cancers studied, so they might be involved in the development of CRC. New therapeutic perspectives based on the selective targeting of the specific population of cells expressing one of those CSCs. OCT-4 expression might be a bad prognostic indicator in rectosigmoid cancer.