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.Colorectal cancer (CRC) constitutes a significant global health burden, leading to over 862,000 deaths globally in 2018. It is the second main cause of cancer mortality in the world and currently stands as the third most common cancer, with a yearly incidence of over one million and eight thousand cases worldwide 1 . Its leading cause of death is due to liver metastasis with a median survival rate of approximately 30 months. Generally, half of the patients with CRC develop tumor recurrences 2 . For early-diagnosed CRC patients, the 5-year survival rates are approximately 90% but this lowers to less than 10% in patients with extensive metastases. Thus, the most effective approach to reduce CRC incidence and its mortality is early detection of colonic lesions 3 . Fortunately, because of implementation and growth of wide spread cancer screening assays, such as colonoscopy as well as increasingly effective therapies, the mortality rate of CRC is lowering in many countries 2 .

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ObjectivesLynch syndrome (LS), a genetically inherited autosomal disorder, increases the incidence of colorectal carcinoma (CRC). We aimed to perform a universal strategy to assess the prevalence and clinicopathological characteristics of early onset CRCs at high risk of LS versus late-onset ones in the Iranian population.SettingA local population-based study from Northeastern Iran.Participants321 consecutive CRCs and pathology specimen screened between 2013 and 2016.Primary and secondary outcome measuresRetrospectively, information regarding the clinical criteria was obtained by interviewing the patients with CRC or, their families. Pathologists tested tumours with immunohistochemistry (IHC) staining of four mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2). Tumours with absent IHC staining of MLH1 were tested for BRAF mutations to exclude sporadic CRCs. Prevalence of early onset CRCs at high risk of LS and familial CRC type X were assessed as primary and secondary outcome measures, respectively.ResultsOf 321 CRCs (13/123 (10.57%), early onset vs 21/198 (10.6%) late-onset) were detected to be MMR-deficient (dMMR). Nine early onset cases and 14 late-onset ones with a loss of MLH1 underwent testing for the BRAF mutation, none of the early onset and four (2.02%) late-onset were recognised as sporadic. The difference in the outcome of IHC-analysis between early and late-onset CRCs at high risk of LS was not statistically significant (p=0.34). Majority of the suspected LS tumours from early onset patients had arisen in distal part (8/11 (72.72%) vs 8/14 (57.14%)), all of which were occurred in the rectum or sigmoid.ConclusionClinically, these findings suggest that in case of limitation for BRAF testing, the practitioner in Iran may consider managing early onset dMMR cases like LS until access to BRAF testing becomes available to them, before germline testing to accurately diagnose LS.

Aims:This study investigated the prognostic value of B type natriuretic peptide (BNP) in acute myocardial infarction (AMI) patients and its relation with left ventricular function and post-myocardial infarction complications.Methods:In this cross-sectional study, plasma BNP level was measured for 42 consecutive patients (mean ± SD: 61.6 ± 10.85 years old) with acute ST elevation myocardial infarction (MI) and 42 healthy, age and gender matched subjects.Result:BNP level in AMI patients were significantly higher than control group (P < 0.001). Regarding to infarct location, the highest BNP level measured in inferoposterior MI (BNP = 4436.63 ± 6188.159 pg/ml) and the lowest one indicated in standalone inferior MI (BNP = 598.83 ± 309.867 pg/ml (P = 0.071). There was significant reverse relation between BNP and EF (P = 0.006, OR = −0.47) and a significant relationship between BNP and killip classification (P = 0.036). There was no significant relation between diastolic and right-ventricular function and BNP level (P = 0.61, P = 0.21). The highest BNP level was detected in LV septal rupture and false aneurysm (P = 0.02) and in ventricular tachycardia, but without significant relationship (P = 0.25).Conclusion:After the onset of AMI, BNP blood level can be used as an important predictor for left ventricular dysfunction, killip classification, early mechanical complications and cardiac death.

O(6)-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that removes alkyl groups from the O(6) position of guanine. MGMT is transcriptionally silenced by promoter hypermethylation in several human neoplasia. We used methylation-specific PCR (MSP) to analyze the MGMT promoter methylation status of 50 glioblastoma tumors. Hypermethylation was detected in 24 of 50 (48%) samples. We also analyzed mutant p53 expression by immunohistochemical analysis of glioblastoma tissue samples. A significant association was found between MGMT methylation and p53 mutation status (p< .05). These results suggested that epigenetic inactivation of MGMT plays an important role in the survival of glioblastoma patients and this inactivated gene involved in p53 mutation.