Oral cancer (OC) ranked as eleventh malignancy worldwide, with the increasing incidence among young patients. Limited understanding of complications in cancer progression, its development system, and their interactions are major restrictions towards the progress of optimal and effective treatment strategies. The system-level approach has been designed to explore genetic complexity of the disease and to identify novel oral cancer related genes to detect genomic alterations at molecular level, through cDNA differential analysis. We analyzed 21 oral cancer-related cDNA datasets and listed 30 differentially expressed genes (DEGs). Among 30, we found 6 significant DEGs including CYP1A1, CYP1B1, ADCY2, C7, SERPINB5, and ANAPC13 and studied their functional role in OC. Our genomic and interactive analysis showed significant enrichment of xenobiotics metabolism, p53 signaling pathway and microRNA pathways, towards OC progression and development. We used human proteomic data for post-translational modifications to interpret disease mutations and inter-individual genetic variations. The mutational analysis revealed the sequence predicted disordered region of 14%, 12.5%, 10.5% for ADCY2, CYP1B1, and C7 respectively. The MiRNA target prediction showed functional molecular annotation including specific miRNA-targets hsa-miR-4282, hsa-miR-2052, hsa-miR-216a-3p, for CYP1B1, C7, and ADCY2 respectively associated with oral cancer. We constructed the system level network and found important gene signatures. The drug-gene interaction of OC source genes with seven FDA approved OC drugs help to design or identify new drug target or establishing novel biomedical linkages regarding disease pathophysiology. This investigation demonstrates the importance of system genetics for identifying 6 OC genes (CYP1A1, CYP1B1, ADCY2, C7, SERPINB5, and ANAPC13) as potential drugs targets. Our integrative network-based system-level approach would help to find the genetic variants of OC that can accelerate drug discovery outcomes to develop a better understanding regarding treatment strategies for many cancer types. Oral Cancer constitutes approximately 90% among all Head and Neck Cancer (HNC) sub-types 1. However, it is more prominent in urban areas of South Asia with a ratio of 15-40% among all cancer types 2. In Pakistan, it ranked as 2nd most prevalent cancer-type, with increasing incidence in the past few years 3,4. The complexity of genetic mechanisms in cancer has been revealed through recent investigations. Many biological systems seem to involved in the development and progression of the cancer. But, the complications in system-interactions are limitedly understood which is a major restriction in developing effective treatments 5. The gene expression studies may help to investigate the differential expression of genes in different biological states, cell cycle stages, subjects or tissues. This gene expression analysis is an important pinpoint for investigating biological processes and their functional disorders. cDNA microarrays were used to ...
Type 2 diabetes mellitus (T2DM) is the most prevailing worldwide health challenge of the 21st century and the 5th leading cause of death worldwide. About 90% of diabetic patients are diagnosed as having T2DM. LPAR1 gene codes LPA protein that is involved in the regulation of many biological processes. In this study, we have investigated the association of single nucleotide polymorphism (SNP) of LPAR1 gene variants rs494605 and rs558347 with T2DM in our local population. This association was analyzed by amplification of the target gene through Tetra ARMS PCR. The study involved 200 participants with equal ration of cases and controls. Both genetic variants of LPAR1 rs494605 and rs558347 have allelic origin T/C. The allelic frequency of LPAR1 was calculated through the Hardy Weinberg Equilibrium. re found that in LPAR1 rs494605 mutant allele, C was 47% in cases compared to controls (39%) and in LPAR1 rs558347, heterozygosity allele (TC) was 46% compared to mutant allele C (13%), while wild T allele was 17% in cases. Many demographic and lifestyle risk factors were significantly associated with LPAR1 gene variants. The heterogeneity of genetic variants with T2DM also showed a strong correlation with obesity, hormonal imbalance, and depression with p-value of 0.001, and 95% confidence interval. Smoking and alcohol consumption are major risk factors of T2DM. Variations in LPAR1 can be used as a biomarker and diagnostic tool for T2DM.
Single nucleotide polymorphisms (SNP) are responsible for genetic mutations. We studied genetic molecular variations and found an association of oral cancer with SNP of Adenylate Cyclase 2 (ADCY2) rs252546 and complement C7 (C7) rs1450656 genes in people of Southern Punjab, Pakistan. The study involves 100 cases of oral cancer and 100 healthy individuals. ADCY2 is found as a membrane-associated enzyme and C7 is involved in innate immunity. The process of genotyping was carried out by Tetra ARMS Primer PCR. The genetic variant of ADCY2 rs252546 has allelic origin G/A and C7 rs1450656 with C/T. The statistical analysis showed that the 51-60 years age group is significantly associated with oral cancer. The allelic frequency of ADCY2 rs252546 and C7 rs1450656 was calculated through Hardy Weinberg equilibrium. The homozygous mutant allele G of ADCY2 was more prevalent in cases and C allelic genotype was equally found in cases and controls. Other demographic and polymorphic studies indicated a significant association of variants of ADCY2 and C7 with oral cancer in the local population of Punjab. Variations in ADCY2 and C7 can be used as potential biomarkers and biological targets for oral cancer management strategies.
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