PIK3CA Mutation Analysis in Iranian Patients with Gastric Cancer

Backgrounda: Aberrant activation of phosphatidylinositol-3 kinases (PI3K)/AKT/mTOR (mammalian target of rapamycin) pathway is a critical event during gastric cancer progression. Selective function of AKT inhibitor AZD5363 in PI3KCA mutant gastric cancer necessitates the assessment of PI3KCA mutations in these patients. Methods: The study included 100 patients with gastric cancer who underwent surgical resection at Imam Reza Hospital, Tehran, Iran, between January 2009 and December 2016. Mutations in codon 1047 of PIK3CA were evaluated by tetra-primer ARMS-PCR and direct sequencing methods. Results: We detected p.H1047R and p.H1047L in eight and three samples, respectively. Also, a significant association was found between PIK3CA mutations and lymphatic invasion. Kaplan-Meier analysis demonstrated no significant differences in overall survival between patients with and without mutations. Conclusion: Our study detected gain-of-function mutations in exon 20 of PI3KCA gene in 11% of gastric cancer patients. Future studies are needed to assess the mutation rate in other regions of this gene to find eligible patients for targeted therapies.

Association of MiR-146a Expression and Type 2 Diabetes Mellitus: A Meta-Analysis.

Although deregulation of miR-146a has been reported in type 2 diabetes repeatedly, the direction of deregulation events (up or down) remained to be inconsistent in literatures. Therefore, in this study we performed a meta-analysis on the possible association between miR-146a expression levels and type 2 diabetes. A systematic literature searching of PubMed, ISI Web of Science and Google Scholar was performed up to the end of September 2016. Finally, a total of 12 studies including 344 diabetic patients and 316 controls were selected for meta-analysis. All statistical analysis was performed using the metafor package with R software. Moreover, publication bias was assessed by Egger's and sensitivity analysis was applied on the meta-analysis. The results are presented as log10 odds ratios (logORs), 95% confidence intervals (CI) with relevant P values. The results revealed that miR-146a was downregulated in type 2 diabetes cases compared with normal subjects (P=0.01, logOR:-4.76, 95% CI:-8.41, -1.11). Furthermore, sub-group analysis showed that the association between miR-146a expression levels and type 2 diabetes in whole blood (P<0.001) and PBMCs (P<0.001) samples were significant. However, this association was not significant in the serum (P=0.67) and plasma (P=0.90) samples. Our finding suggests that miR-146a downregulation could be associated with type 2 diabetes susceptibility. Further investigations with larger sample size are required to evaluate this association in the type 2 diabetes pathogenesis.