In the current study, the prognostic and predictive values of serum transforming growth factor-β1 (TGF-β1), insulin-like growth factor I (IGF-I)/IGF-I receptor (IGF-IR) and vascular endothelial growth factor-A (VEGF-A) were evaluated in triple-negative and non-triple-negative breast cancer (TNBC and non-TNBC). The aim was to identify a group of serological biomarkers and to identify possible candidates for targeted therapy in patients with TNBC and non-TNBC. Protein levels of TGF-β1, IGF-I/IGF-IR and VEGF-A in the serum were measured in 43 TNBC, 53 non‑TNBC and 20 normal control participants using quantitative ELISA assays. Results were correlated against standard prognostic factors, response to treatment and survival. TNBC was identified to be associated with poor prognosis and serum levels of VEGF-A and IGF/IGF-IR were significantly higher in the TNBC group compared with the non-TNBC group. IGF-IR and VEGF-A overexpression was observed to be correlated with TGF-β1 expression and all of the markers investigated were associated with metastasis and disease progression. In the multivariate analysis, VEGF-A, IGF-I and IGF-IR were observed to be independent predictors for overall survival, whereas TGF-β1 and lymph node status were identified as independent predictors for disease-free survival. The overall response rate was significantly lower in patients with TNBC and those with high levels of TGF-β1, IGF-I/IGF-IR and VEGF-A. In view of the present results, it was concluded that TGF-β1, IGF-I/IGF-IR and VEGF-A overexpression is associated with the presence of aggressive tumors, which exhibit an increased probability of metastasis, a poor response to treatment and reduced survival rate. This indicates that VEGF-A, IGF-IR and IGF-I have the potential to be used as surrogate biomarkers and are promising candidates for targeted therapy, particularly in patients with TNBC.

AIM: To assess the role of circulating tumor cells (CTCs) and cancer stem cells (CSCs) in hepatitis C virus (HCV)-associated liver disease. METHODS: Blood and/or tissue samples were obtained from HCV (genotype 4)-associated hepatocellular carcinoma patients (HCC; n = 120), chronic hepatitis C patients (CH; n = 30) and 33 normal control subjects (n = 33). Serum levels of alpha-fetoprotein (AFP), alkaline phosphatase, and alanine and aspartate aminotransferases were measured. Cytokeratin 19 (CK19) monoclonal antibody was used to enumerate CTCs, and CD133 and CD90 were used to enumerate CSCs by flow cytometry. The expression levels of the CSCs markers (CD133 and CD90) as well as telomerase, melanoma antigen encoding gene 1 (MAGE1) and MAGE3 were assessed by RT-PCR and quantitative real-time polymerase chain reactions. The number of CTCs and/or the expression levels of CK19, CD133, telomerase, MAGE1 and MAGE3 were correlated to the standard clinicopathologic prognostic factors and disease progression. RESULTS: Levels of AFP, alkaline phosphatase and aspartate aminotransferase were significantly different among the HCC, CH and control groups (P < 0.001), whereas alanine aminotransferase differed significantly between patient (HCC and CH) and control groups (P < 0.001). At the specified cutoff values determine by flow cytometry, CK19 (49.8), CD90 (400) and CD133 (73) were significantly higher in the blood of HCC patients compared to those in the CH and control groups (P < 0.001). On the other hand, CD133 at a 69.5 cutoff was significantly higher in the CH compared to the control group (P≤ 0.001). Telomerase, MAGE1 and MAGE3 RNA were expressed in 55.71%, 60.00% and 62.86% of the HCC patients, respectively, but were not detected in patients in the CH or control groups, which were statistically significant (Ps < 0.001). The expression levels of telomerase, CD90, MAGE3, CD133 and CK19 were all significantly associated with high tumor grade and advanced stage in HCC patients (all Ps < 0.05). CONCLUSION: CTC counts and AFP, CK19, telomerase, and MAGE1/MAGE3 expression predict disease progression in patients with HCV, whereas telomerase, MAGE3, CD90, CD133 and CK19 are prognostic markers in HCC.

Several studies have reported the role of CYP2A6 genetic polymorphisms in smoking and lung cancer risk with some contradictory results in different populations. The purpose of the current study is to assess the contribution of the CYP2A6*2 rs1801272 and CYP2A6*9 rs28399433 gene polymorphisms and tobacco smoking in the risk of lung cancer in an Egyptian population. A case-control study was conducted on 150 lung cancer cases and 150 controls. All subjects were subjected to blood sampling for Extraction of genomic DNA and Genotyping of the CYP2A6 gene SNPs (CYP2A6*2 (1799 T > A) rs1801272 and CYP2A6*9 (− 48 T > G) rs28399433 by Real time PCR. AC and CC genotypes were detected in CYP2A6*9; and AT genotype in CYP2A6*2. The frequency of CYP2A6*2 and CYP2A6*9 were 0.7% and 3.7% respectively in the studied Egyptian population. All cancer cases with slow metabolizer variants were NSCLC. Non-smokers represented 71.4% of the CYP2A6 variants. There was no statistical significant association between risk of lung cancer, smoking habits, heaviness of smoking and the different polymorphisms of CYP2A6 genotypes. The frequency of slow metabolizers CYP2A6*2 and CYP2A6*9 are poor in the studied Egyptian population. Our findings did not suggest any association between CYP2A6 genotypes and risk of lung cancer.

Cytochrome P450 CYP1A1 helps detoxify the potential carcinogens in tobacco smoke, it was reported that polymorphisms in the coding gene result in variation in the expression and activity levels which alter metabolism and clearance of carcinogens and therefore modify cancer risk. In this work, we aimed to identify CYP1A1 gene polymorphisms associated with lung cancer in Egyptian population and to examine the interaction effect with Tobacco smoking in modulating disease risk. A case–control study was conducted on 150 unrelated lung cancer patients and 150 unrelated control subjects. Genomic DNA was extracted and sequencing analysis of CYP1A1 gene was performed on ABI PRISM 3100 genetic analyzer. Three variants in CYP1A1 gene were identified in heterozygous forms in lung cancer patients I462V, T461N and I286T. A combined variant T461N/ I462V associated with lung cancer and those who carried this variant were 2-times more likely to develop lung cancer (OR = 2.03, 95% CI = 1.81-2.29, P = 0.04), specially the non-small cell type (NSCLC) (OR = 2.20, 95% CI = 1.93–2.50, P = 0.02). Wild type was more frequent among smoker controls (83.3%) compared to smoker lung cancer patients (54.8%), P = 0.03. Association studies to examine the interaction effect of identified variants with Tobacco smoking in modulating disease risk showed no significant associations. Identified polymorphisms showed no significant implication on the stage or the prognosis of the disease. Our findings support that CYP1A1 polymorphisms play a role in the pathogenesis of lung cancer. In Egyptian population, CYP1A1 I462V, T461N and I286T variants were identified among lung cancer patients and combined T461N/ I462V was a risk variant for NSCLC in non smokers.