PTEN-induced putative kinase 1 (PINK1) down-regulation in breast cancer samples in association with mitotic rate

PINK1 codes for a serine/threonine-protein kinase located in the mitochondria. This protein contributes in the pathophysiology of both neurodegenerative diseases and cancer. Its transcription has been shown to be regulated by a natural occurring antisense (AS) RNA named PINK1-AS. We examined expression levels of PINK1 and PINK1-AS in 54 breast cancer specimens versus their nearby non-cancerous tissues. We found significant down-regulation of PINK1 in tumoral tissues compared with nearby tissues (P = .003). Yet, expression of PINK1-AS was not remarkably different between tumoral tissues and nearby tissues. Relative expression of PINK1 was associated with mitotic rate (P = .03). We also found trends toward over-expression of PINK1 in younger patient compared with older patients (P = .09) and in grade 2 tumors compared with grade 3 ones (P = .08). The current study delivers further evidences for contribution of PINK1 in the pathophysiology of breast cancer and highlights the context-dependent properties the encoded protein

Suppressor of cytokine signaling (SOCS) genes are downregulated in breast cancer

Abstract Background The suppressor of cytokine signaling (SOCS) family of proteins are inhibitors of the cytokine-activated Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway. We aimed at evaluation of expression of SOCS genes in breast cancer. Methods We evaluated expression of SOCS1–3 and SOCS5 genes in breast cancer samples compared with the corresponding adjacent non-cancerous tissues (ANCTs). Results All assessed SOCS genes were significantly downregulated in tumoral tissues compared with ANCTs. SOCS1 and SOCS2 genes were significantly overexpressed in higher grade samples, but SOCS3 had the opposite trend. Significant correlations were found between expression levels of SOCS genes. The SOCS1 and SOCS2 expression levels had the best specificity and sensitivity values respectively for breast cancer diagnosis. Conclusion The current study provides further evidence for contribution of SOCS genes in breast cancer

IVS8 Polyt and M470V Polymorphisms in Healthy Individuals and Cystic fibrosis Patients in Mazandaran Province, Iran

Background: Cystic fibrosis (CF) is a multiorgan autosomal recessive disorder. As CF is highly heterogeneous in Iran and many mutations have a low frequency, routine molecular diagnostic methods are not very efficient. The use of highly polymorphic intragenic markers not only can facilitate phenotype prediction in prenatal diagnosis by gene tracking, but also can lead to the demonstration of possible associations between haplotypes and specific mutations. We determined IVS8 polyT and M470V polymorphisms in exon 10 of CFTR gene in this case-control study. Methods: Polymorphisms of IVS8 polyT in 53 patients with CF were referred to Amirkola children&apos;s Hospital of Babol University of Medical Sciences, 2007 to 2011 and 49 fertile healthy individuals were determined by reverse dot blot method. M470V polymorphism was analyzed by PCR-RFLP. Results: In IVS8 polyT study, T7 was the most frequent allele in healthy individuals than patients with CF (respectively, 82.8% Vs. 77.2%). T9 was more abundant in patients with CF than normal individuals (respectively, 21.7% Vs. 7.4%, P=0.005). T9/T9 genotype was more frequent in patients than healthy individuals (respectively, 15.1% and 2%, P=0.032). Study for M470V polymorphism showed that M/V was the most common genotype in normal individuals and patients with CF (respectively, 49% and 40.4%). M-T9 haplotype was highly associated with the disease in both patients with CF and normal individuals (respectively, 19.1% and 2.4%, (P<0.001 Conclusion: The allelic distribution and heterozygosity results suggest that both M470V and IVS8 polyT can be helpful in the prenatal diagnosis of CF in Northern Iranians with a positive family history of the disease

Circulating free DNA concentration as a marker of disease recurrence and metastatic potential in lung cancer

Abstract Background Plasma circulating cell-free (cf) DNA is regarded as a source of tumor DNA. Based on availability of blood tissue for the purposes of early detection of cancer and patients’ follow-up, several studies have evaluated concentration of cf DNA in cancer patients in association with tumor features. In the present study, we assessed concentration of cf DNA in lung cancer patients with two commercial kits (MN and QIAGEN) to find whether it can be used as a prognostic biomarker. Results Primary cf DNA concentrations as measured by QIAGEN kit was significantly higher in patients who died in the follow-up period compared with alive patients (P = 0.007). Moreover, the concentrations as measured by both methods were higher in patients who experienced recurrence in the follow-up period compared with patients without recurrence (P = 0.008 and 0.007 for MN and QIAGEN kits respectively). Significant associations were also found between cf DNA concentrations and tumor stage (P = 0.005 and 0.02 for MN and QIAGEN kits respectively). Notably, cf DNA concentration was higher in metastatic tumors compared with non-metastatic tumors in association with number of involved organs. Based on the AUC values, both kits could differentiate metastatic cancers from non-metastatic ones with accuracy of 98%. Conclusions The current study highlights the accuracy of cf DNA concentrations for prediction of disease course in lung cancer patients