Circulating let-7e-5p, miR-106a-5p, miR-28-3p, and miR-542-5p as a Promising microRNA Signature for the Detection of Colorectal Cancer.

Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model's performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.

Apolipoprotein E polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) infection is responsible for a chronic liver inflammation, which may cause end-stage liver disease and hepatocellular carcinoma. Apolipoprotein E (protein: ApoE, gene: APOE), a key player in cholesterol metabolism, is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver damage. AIM: To determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation (OLT). METHODS: This was a cohort study in which 179 patients, both genders and aged 34-70 years, were included before or after (up to 10 years follow-up) OLT. Liver injury severity was assessed using different criteria, including METAVIR and models for end-stage liver disease. APOE polymorphisms were analyzed by quantitative real-time polymerase chain reaction. RESULTS: The APOE3 allele was the most common (67.3%). In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant, the degree of severe inflammation (A3F4, 0.0%) was significantly less frequent than in patients with minimal and moderate degree of inflammation (≤ A2F4, 16.2%) P = 0.048, in patients carrying the APOE4 allele when compared to non-APOE4. In addition, a significant difference was also found (≤ A2F4, 64.4% vs A3F4, 0.0%; P = 0.043) and (A1F4, 57.4% vs A3F4, 0.0%; P = 0.024) in APOE4 patients when compared to APOE3 carriers. The fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis (F2) (P = 0.006). CONCLUSION: Our results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.

Metabolic syndrome, diabetes and inadequate lifestyle in first-degree relatives of acute myocardial infarction survivors younger than 45 years old.

BACKGROUND: A premature myocardial infarction (PMI) is usually associated with a familial component. This study evaluated cardiovascular risk factors in first-degree relatives (FDR) of patients with PMI not presenting the familial hypercholesterolemia phenotype. METHODS: A cross-sectional study comprising FDR of non-familial hypercholesterolemia patients who suffered a myocardial infarction <45-years age matched for age and sex with individuals without family history of cardiovascular disease. Subjects were evaluated for presence of the metabolic syndrome and its components, lifestyle, statin therapy, and laboratory parameters. RESULTS: The sample was composed of 166 FDR of 103 PMI patients and 111 controls. The prevalence of smoking (29.5 vs. 6.3%; p < 0.001), prediabetes (40.4 vs. 27%; p < 0.001), diabetes (19.9 vs. 1.8%; p < 0.001), metabolic syndrome (64.7 vs. 36%; p < 0.001), and dyslipidemia (84.2 vs. 31.2%; p = 0.001) was greater in FDR. There was no difference on the prevalence of abdominal obesity between groups. In addition, FDR presented higher triglycerides (179.0 ± 71.0 vs. 140.0 ± 74.0 mg/dL; p = 0.002), LDL-cholesterol (122.0 ± 36.0 vs. 113.0 ± 35 mg/dL; p = 0.031), non-HDL-cholesterol (157.0 ± 53.0 vs. 141.0 ± 41.0 mg/dL; p = 0.004), and lower HDL-cholesterol (39.0 ± 10.0 vs. 48.0 ± 14.0 mg/dL; p < 0.001) than controls. Thyrotropin levels (2.4 ± 1.6 vs. 1.9 ± 1.0 mUI/L; p = 0.002) were higher in FDR. The risk factor pattern was like the one of index cases. Only 5.9% (n = 10) of FDR were in use of statins. CONCLUSIONS: FDR of non-familial hypercholesterolemia patients with PMI presented an elevated prevalence of metabolic abnormalities, inadequate lifestyle and were undertreated for dyslipidemia.