Anti-GRM5 monoclonal antibody, clone T86-44 [FITC]

Background: Oral cancer represents the third most prevalent form of malignancy in developing countries and the eight most common form of cancer in developed countries. Alcohol and tobacco users are most affected by oral cancers and 90% of them are OSCC in adult males. In some provinces in Iran such as Sistan and Baluchestan, its prevalence is higher compared to other provinces. One of the primary neurotransmitter in the central nervous system is systemic glutamate, which is a major excitatory neurotransmitter. Glutamate signaling has been involved in various non-neuronal cancer processes. The aim of this research was to highlight the association between DNA methylation of the glutamate receptor genes and their expression pattern in pathogenesis of OSCC. Materials and methods: Genomic DNA was isolated from 83 OSCC paraffin-embedded tissues (mean age: 59.67 +/- 16.08) and 80 normal samples (mean age: 50.15 +/- 16.69). Promoter methylation status of glutamate receptors including GRM5, GRM2 and GRIA3 genes were carried out by Methylation Specific PCR technique (MSP). We also investigated the mRNA expression levels of these genes in 15 paraffin-embedded patients and healthy samples using real-time PCR techniques. Result: DNA methylation analysis showed statistically significant differences in the cases in comparison with healthy controls. Our data showed that the promoters of GRM2 and GRIA3 were methylated in the cases. For GRM2 (MM: OR = 0.32; 95% CI = 0.02-3.90; p-value = .37; MU: OR = 8.0; 95% CI = 1.37-47.34; p-value = .02) and GRIA3 (MM: OR = 47.19; 95% CI = 4.61-483.0; p-value = .001; MU: OR = 1.45; 95% CI = 0.35-5.89; p-value = .6). However, methylation of GRM5 promoter was not statistically different in the cases and healthy controls, GRM5 (MM: OR = 0.9; 95% CI = 0.14-5.71; p-value = 0.9; MU: OR = 1.83; 95% CI = 0.33-10.09; p-value = .4). In addition, the evaluation of mRNA expression levels of GRM2, GRIA3 and GRM5 were remarkably different in patients and healthy controls (p < .0001). Summarily, the aim of this study was to assess the methylation and expression pattern of GluR genes and the risk of OSCC. We are of the presupposition that methylation and expression statuses of the chosen genes, GRM5, GRM2 and GRIA3 might be significant biomarkers for OSCC.

Alcohol use disorder (AUD) is suggested to have polygenic risk factors and also exhibits neurological complications, strongly encouraging a translational study to explore the associations between aggregates of genetic variants and brain function alterations related to alcohol use. In this study, we used a semiblind multivariate approach, parallel independent component analysis with multiple references (pICA-MR) to investigate relationships of genome-wide single nucleotide polymorphisms with alcohol cue-elicited brain activations in 315 heavy drinkers, where pICA-MR assesses multiple reference genes for their architecture and functional influences on neurobiological conditions. The genetic component derived from the cAMP-response element-binding protein and -brain derived neurotrophic factor (CREB-BDNF) pathway reference was significantly associated (r=-0.38, P=3.98 x 10(-12)) with an imaging component reflecting hyperactivation in precuneus, superior parietal lobule, and posterior cingulate for drinkers with more severe alcohol dependence symptoms. The highlighted brain regions participate in many cognitive processes and have been robustly implicated in craving-related studies. The genetic factor highlighted the CREB and BDNF references, as well as other genes including GRM5, GRM7, GRID1, GRIN2A, PRKCA, and PRKCB. Ingenuity Pathway Analysis indicated that the genetic component was enriched in synaptic plasticity, GABA, and protein kinase A signaling. Collectively, our findings suggest that genetic variations in various neural plasticity and signaling pathways partially explain the variance of precuneus reactivity to alcohol cues which appears to be associated with AUD severity. Hum Brain Mapp 36:3007-3019, 2015. (c) 2015 Wiley Periodicals, Inc.