Significance of cancer testis-associated antigens (SPAG9 and FBXO39) in colon cancer.

Background: Cancer testis antigens (CTA) are normally expressed in immune privileged tissues such as the testis. They are considered tumor-associated antigens because they are specifically expressed in different cancers. Their distinct nature rendered them appealing targets for cancer diagnosis, prognosis. and immunotherapy. We aimed to identify the association of two CTA genes with colon cancer (CC) in a cohort of Egyptian patients. Methods: We measured the relative gene expression levels of two CTAs: SPAG9 and FBXO39 in colonic tumor tissue and adjacent normal-appearing mucosa in 50 newly diagnosed colon cancer patients by real-time reverse transcription polymerase chain reaction. Gene expression was also studied in relation to demographic and pathological criteria. Results: SPAG9 and FBXO39 were overexpressed in 22% and 40% of cases, respectively. Overexpression of both genes was evident in 14% of cases. We report the significant expression of FBXO39 (P < 0.01) in tumor tissue compared to normal tissue. SPAG9 was significantly increased in large sized tumors compared to smaller sized tumors. Otherwise, there was no significant association between gene expression and the evaluated clinicopathological features (P > 0.05). Conclusions: SPAG9 and FBXO39 are possible CC diagnostic biomarkers. Further studies are warranted to validate our findings.

Significance of expression of pyrimidine metabolizing genes in colon cancer.

BACKGROUND AND STUDY AIMS: The reprogramming of metabolic pathways in tumour cells is a crucial step to meet the increased requirements for their own growth. This process occurs through alterations in gene expression, polymorphisms, and epigenetic dysregulation of a number of metabolic genes. Several metabolic enzymatic pathways such as pyrimidine-metabolizing enzymes have been implicated in tumorigenesis and tumor progression. PATIENTS AND METHODS: We measured the relative expression levels of three pyrimidine-metabolizing genes-thymidylate synthase (TYMS), thymidine phosphorylase (TYMP), and dihydropyrimidine dehydrogenase (DPYD)-in tumor tissue and adjacent normal-appearing mucosa in 50 colon cancer (CC) patients using real-time reverse-transcription polymerase chain reaction. Gene expression was also studied in relation to demographic and pathological criteria. RESULTS: The gene expression levels of both TYMS and TYMP were significantly higher in tumor tissue than normal adjacent tissue. Further, they showed an agreeable level of diagnostic performance as a means to discriminate between normal and tumor tissue; TYMS had high specificity (94%) but moderate sensitivity (60%), while TYPM showed average sensitivity (70%) and specificity (76%). Although DPYD expression was lower in tumor tissue than paracancerous tissue, this level did not reach the statistical significance. TYMS expression was significantly higher in moderately and poorly differentiated tumors than in well-differentiated ones. There was no significant association between gene expression and the remaining clinicopathological criteria (e.g., age, sex, tumor location, and metastasis). We found a positive correlation between the gene expression levels of TYMS and DPYD. CONCLUSION: TYMS and TYMP messenger RNA levels seem to be plausible indicators in the diagnosis of CC, although further studies are warranted for validation.

Comparison of Serum Trefoil Factor-3 to Endoscopy in Diagnosing Helicobacter Pylori Associated Gastric Ulcer.

BACKGROUND AND AIM OF THE WORK: Helicobacter pylori-associated gastric ulcer (H.pylori-GU) is a serious condition, not only because H.pylori is identified as a grade 1 carcinogen but also because GU is a precancerous condition. Identification and treatment of H.pylori-GU may prevent the sequential progression of dysplasia to carcinoma. Trefoil factor 3 (Tf3) has been implicated in gastric mucosal repair. We compared serum Tf3 to gastric endoscopy in diagnosing H.pylori-GU. SUBJECTS AND METHODS: The study included eighty patients suffering from H.pylori induced gastritis, forty of which presented with GU. Gastric endoscopy with slide urease test was used to diagnose H.pylori-GU. Serum Tf3 level was determined using an enzyme immunoassay in all patients as well as thirty healthy volunteers. RESULTS: Serum Tf3 showed a significant stepwise decrease among the studied groups. It was significantly lower in patients compared to the control group (p<0.001). Furthermore, it was lower in those with GU compared to those without GU (p=0.023). Based on a receiver operating characteristic curve generated cut off value of 2.4 ng/mL, the diagnostic performance of serum Tf3 as a biomarker of H.pylori-GU revealed a diagnostic specificity of 42.5%, sensitivity of 67.5%, positive and negative predictive values of 54% and 56.67% respectively. CONCLUSION: Although serum Tf3 showed significant variation in H.pylori-GU, further studies are warranted to confirm its role in the pathogenesis of gastric ulcers.
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Aberrant methylation of promoter region of SPINT2/HAI-2 gene: an epigenetic mechanism in hepatitis C virus-induced hepatocarcinogenesis.

BACKGROUND: Epigenetic changes, including DNA methylation, are recognized as one of the potential mechanisms involved in the pathogenesis of hepatocellular carcinoma (HCC). AIMS: We aimed to study the methylation status of the promoter region of Serine peptidase inhibitor/hepatocyte growth factor activator inhibitor type 2 (SPINT2/HAI-2) tumor suppressor gene in hepatitis C virus (HCV)-infected cirrhotic patients with and without HCC. METHODS: Methyl-specific polymerase (MSP) chain reaction was used to detect CpG methylation of the SPINT2/HAI-2 gene promoter in peripheral blood samples of 30 HCC and 50 HCV cirrhotic cases, along with 50 normal individuals. RESULTS: Aberrant methylation showed a stepwise increase in frequency from 40% in controls to 64% in HCV cirrhotics, and 66.7% in HCC cases with a significant difference among the studied groups (p=0.021). The combined patient groups had an increased risk of aberrant methylation with an odds ratio (OR) of 2.52, a 95% confidence interval (CI) of 1.23-5.14, and a p-value of 0.05 that became more statistically significant after adjusting for age (OR=2.4, 95% CI=1.13-5.26, p-value=0.012), thereby confirming the association between HCV infection and aberrant methylation. CONCLUSIONS: Our study highlights the role of promoter hypermethylation in the multistep process of hepatocarcinogenesis, providing potential clinical applications in diagnosis and prognosis.

Association of DNA repair genes XRCC1 (Arg399Gln), (Arg194Trp) and XRCC3 (Thr241Met) polymorphisms with the risk of breast cancer: a case-control study in Egypt.

UNLABELLED: Various DNA damage, induced by endogenous and exogenous factors, is handled through DNA repair pathways such as X-ray repair cross-complementing protein (XRCC). Genetic variations in these pathways may have a joint or additive effect on various types of cancer, including the risk of breast cancer (BC). AIM: To evaluate the association of three single-nucleotide polymorphisms (SNPs) Arg399Gln, Arg194Trp, and Thr241Met in DNA repair genes XRCC1 and XRCC3 on the risk of BC, and to assess their interaction with risk factors and prognostic markers in a case-control study in Egypt. METHODS: We detected the studied SNPs using polymerase chain reaction-restriction enzyme polymorphism (PCR-RFLP) in peripheral blood from 100 BC patients and 75 healthy females. RESULTS: The dominant model of inheritance of Arg399Gln and Arg194Thr revealed an increase in BC risk of odds ratio (OR) of 3.56, 95% confidence interval (CI)=1.22-10.39, p=0.017 and OR: 4.45, 95% CI=2.35-8.45, p<0.001 respectively. However, there was no clear interaction between the studied SNPs and the known risk factors, or tumor criteria. No association between the Thr241Met genotype and BC risk was observed. CONCLUSION: XRCC1 Arg399Gln and Arg164Trp variant genotypes are associated with an increased risk of BC in Egyptian females.