Crosstalk between DNA methylation and gene expression in colorectal cancer, a potential plasma biomarker for tracing this tumor.

Colorectal cancer (CRC), the second leading cause of cancer mortality, constitutes a significant global health burden. An accurate, noninvasive detection method for CRC as complement to colonoscopy could improve the effectiveness of treatment. In the present study, SureSelectXT Methyl-Seq was performed on cancerous and normal colon tissues and CLDN1, INHBA and SLC30A10 were found as candidate methylated genes. MethyLight assay was run on formalin-fixed paraffin-embedded (FFPE) and fresh case and control tissues to validate the methylation of the selected gene. The methylation was significantly different (p-values < 2.2e-16) with a sensitivity of 87.17%; at a specificity cut-off of 100% in FFPE tissues. Methylation studies on fresh tissues, indicated a sensitivity of 82.14% and a specificity cut-off of 92% (p-values = 1.163e-07). The biomarker performance was robust since, normal tissues indicated a significant 22.1-fold over-expression of the selected gene as compared to the corresponding CRC tissues (p-value < 2.2e-16) in the FFPE expression assay. In our plasma pilot study, evaluation of the tissue methylation marker in the circulating cell-free DNA, demonstrated that 9 out of 22 CRC samples and 20 out of 20 normal samples were identified correctly. In summary, there is a clinical feasibility that the offered methylated gene could serve as a candidate biomarker for CRC diagnostic purpose, although further exploration of our candidate gene is warranted.

Obesity, diabetes and the risk of colorectal adenoma and cancer.

BACKGROUND: Colorectal cancer (CRC) is the fourth most commonly diagnosed gastrointestinal (GI) malignancy and the third leading cause of cancer-related death worldwide. In the current case-control study, an association between diagnosis of CRC, obesity and diabetes was investigated. METHODS: Demographic characteristics, colonoscopy reports, history of drug, smoking, and medical history were collected from patients referred to a colonoscopy unit. The location, size and number of the polyps were recorded during the colonoscopy. Statistically, t-test was conducted for mean comparison for the groups. Pearson's chi-squared test (χ2) was applied to categorize variables. Five classification methods based on the important clinicopathological characteristics such as age, BMI, diabetes, family history of colon cancer was performed to predict the results of colonoscopy. RESULTS: Overall, 693 patients participated in this study. In the present study, 115 and 515 patients were evaluated for adenoma/adenocarcinoma and normal colonoscopy, respectively. The mean age of patients positive for adenoma or adenocarcinoma were significantly higher than the negative groups (p value < 0.001). Incidence of overweight and/or obesity (BMI > 25 kg/m2) were significantly higher in adenoma positive patients as compared to controls (49.9 and 0.9% respectively, p value = 0.04). The results also demonstrated a significant association between suffering from diabetes and having colon adenoma (OR = 1.831, 95%CI = 1.058-3.169, p value = 0.023). The experimental results of 5 classification methods on higher risk factors between colon adenoma and normal colonoscopy data were more than 82% and less than 0.42 for the percentage of classification accuracy and root mean squared error, respectively. CONCLUSIONS: In the current study, the occurrence of obesity measured based on BMI and diabetes in the adenoma positive patient group was significantly higher than the control group although there was no notable association between obesity, diabetes and adenocarcinoma.

A novel large germ line deletion in adenomatous polyposis coli (APC) gene associated with familial adenomatous polyposis.

BACKGROUND: Familial adenomatous polyposis (FAP) is a familial colorectal cancer predisposition syndrome characterized by the development of numerous colorectal polyps, which is inherited in an autosomal dominant manner. FAP is caused by germ line mutations in adenomatous polyposis coli (APC) gene. Here, we described the identification of a causative APC gene deletion associated with FAP in an Iranian family. METHODS: Diagnosis of FAP was based on clinical findings, family history, and medical records (colonoscopy and histopathological data) after the patients were referred to Reza Radiotherapy and Oncology Center, Iran, for colonoscopy. Blood samples were collected, and genomic DNA was extracted. APC mutation screening was conducted by target next-generation sequencing and quantitative real-time PCR. RESULTS: A novel heterozygous large deletion mutation, c.(135+1_136-1)_(*2113+1_*2114-1) spanning exon 3 to 16 [EX3_16 DEL] of APC gene (GenBank Accession# MG712911), was detected in a proband and all her affected relatives in five generations, which was absent in unaffected family members and normal controls. CONCLUSIONS: This novel deletion is the first report, describing the largest deletion of APC gene. Our novel finding contributes to a more comprehensive database of germ line mutations of APC gene that could be used in medical practice for the molecular diagnosis, risk assessment susceptibility of the disease for the FAP patients.

Serum gastrin 17, pepsinogen I and pepsinogen II in atrophic gastritis patients living in North-East of Iran.

BACKGROUND: Gastric carcinoma is the second most common cause of cancer-related death in Iran. It is well-known that atrophic gastritis is a major risk factor for gastric cancer, which leads to variations in the serum levels of gastrin 17 (G-17), pepsinogen I (P-I), and pepsinogen II (P-II). The aim of this study was to investigate the diagnostic accuracy of these serum biomarkers in the early detection of atrophic gastritis. MATERIALS AND METHODS: A total of 132 dyspeptic patients underwent upper endoscopy and biopsies were taken. The biopsy specimens were evaluated as the gold standard according to operative link for gastritis assessment staging system. Serum levels of G-17, P-I, and P-II were investigated using enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) analysis was used to calculate the diagnostic indices and optimal cut-off values using Statistical Package for the Social Sciences SPSS statistical software. RESULTS: A total of 67 men and 65 women were analyzed, among which 48 (36.4%) had atrophic gastritis. The mean age was 45.8 (±15.8) years. ROC curve analysis demonstrated that the biomarkers (including pepsinogen I/II [P-I/II] ratio), except for P-I, are diagnostically significant in detecting gastric atrophy. The area under the curve (95% confidence interval [CI]) for G-17, P-I, P-II, and P-I/II ratio were 0.65 (0.55-0.76), 0.42 (0.32-0.53), 0.62 (0.52-0.72), and 0.61 (0.50-0.72), respectively. However, the diagnostic indices were low (sensitivity <50%, specificity < 90%). The prevalence of Helicobacter pylori infection was significantly higher in patients with atrophy against those without atrophy (75.0% vs. 57.4%, P value < 0.0001). CONCLUSION: In the studied population, the serum biomarkers of atrophic gastritis are not useful screening tests due to their low sensitivity.