A machine learning approach identified a diagnostic model for pancreatic cancer through using circulating microRNA signatures.

Late diagnosis of pancreatic cancer (PC) due to the limited effectiveness of modern testing approaches, causes many patients to miss the chance of surgery and consequently leads to a high mortality rate. Pivotal improvements in circulating microRNA expression levels in PC patients make it possible to diagnose and treat patients at earlier stages. A list of circulating miRNAs was identified in this study using bioinformatics methods in association with pancreatic cancer through analyzing four GEO microarray datasets. The value of top miRNAs was then assessed via using a machine learning method. Taking the advantage of a combinatorial approach consisting of Particle Swarm Optimization (PSO) + Artificial Neural Network (ANN) and Neighborhood Component Analysis (NCA) iterations on a collection of top differentially expressed circulating miRNAs in PC patients, facilitated ranking them by significance. MiRNA's functional analysis in the final index was performed by predicting target genes and constructing PPI networks. Remarkably, the final model consist of miR-663a, miR-1469, miR-92a-2-5p, miR-125b-1-3p and miR-532-5p showed great diagnostic results on investigated cases and the validation set (Accuracy: 0.93, Sensitivity: 0.93, and Specificity: 0.92). Kaplan-Meier survival assessments of the top-ranked miRNAs revealed that three miRNAs, hsa-miR-1469, hsa-miR-663a and hsa-miR-532-5p, had meaningful associations with the prognosis of patients with pancreatic cancer. This miRNA index may serve as a non-invasive and potential PC diagnostic model, although experimental testing is needed.

Association between TNF-α rs1799964 and RAF1 rs1051208 MicroRNA binding site SNP and gastric cancer susceptibility in an Iranian population.

AIM: The aim of this study was to find the relationship between rs1799964 in TNF-α gene as well as rs1051208 of RAF1 gene SNPs on GC in an Iranian population. BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer-related death worldwide after lung cancer. Tumor necrosis factor (TNF) is one of the most important factors in the pathogenesis of this cancer. Single nucleotide polymorphisms have a principle role in gene expression of TNF-α and miRNAs which may lead to gastric cancer. METHODS: In a case-control study, we investigated the risk of GC in 198 Iranians. For this purpose, 5 mL of peripheral blood was collected in EDTA -containing tube and genomic DNA was isolated. Genotyping of SNPs was also performed by PCR-RFLP; to approve the outcome, 10% of genotyping results with RFLP were sequenced. RESULTS: The comparison between case and control groups revealed a significant association between the rs1051208 C allele of RAF1 gene and GC (P = 0.04). We did not observe any remarkable association between TNF-α -1031 in gastric cancer patients and the healthy control group. CONCLUSION: The results indicated that C allele in RAF1 gene plays a role in susceptibility to gastric cancer. Therefore, SNPs are among notable biomarkers for predicting susceptibility to dreadful diseases, especially cancers.

Frameshift Mutations (Deletion at Codon 1309 and Codon 849) in the APC Gene in Iranian FAP Patients: a Case Series and Review of the Literature.

Familial adenomatous polyposis (FAP) is responsible for <1% of colorectal cancer (CRC) cases and is inherited an autosomal dominant trait. Patients generally present hundreds to thousands of adenomas and develop colorectal cancer by age 35- 40 if left untreated. Here we report four patients with germline frameshift mutation (small deletion) at exon 15 of adenomatous polyposis coli (APC) tumor suppressor gene. Peripheral blood samples were collected from patients and Exon 15 of the APC gene was studied by direct sequencing after genomic DNA extraction. Four frameshift mutations were detected. Two patients had 5 bp deletion, c.3927_3931delAAAGA and two siblings presented deletion at codon 849 (c.2547_2548delTA p.Asp849fsX62). This study was the first report of genetic screening in Iranian FAP patients. In contrast to other studies we revealed that one patient with mutation at codon 1309 had an attenuated phenotype.