Combined Analysis of Genes
CDH1 which is also known as E-cadherin founds on chromosome 16q22.1 and supports cell–cell adhesion by forming adhesive junctions in epithelial cells for inititating and preserving intercellular adhesion, cell polarirty, intercellular signalling and structure of tissue. There have many reports that emphasize on a fact that CDH1 is being expressed in several types of cancer. And if the CDH1 is not present , it is adamantly indicating that there might be changes in cell’s function and motility. It was also observed that antagonistic gesture of OSCC has its connection with the lesser expression of CDH1 (E-cadherin). It was identified that the chances of tumour avalanche which is a known property of cancerous cells “metastasis” could happen if mutation occurs or if gene expresses less. Promoter methylation of CDH1 is found to be 17–85% in oral-cavity tumours[Supic G et.al(2011), Chang et.al(2002), Kordi-Tamandani DM et.al(2010), Shaw RJ et.al (2006)] .
MGMT could be a detoxifying agent of desoxyribonucleic acid adducts. It’s vital in preventing alkylation and, thus, might be prophetic of chemosensitivity. During a massive survey 44 of the many neoplasm sorts , MGMT was alkyl in up to thirty eighth of primary colon cancers, gliomas , and head and neck cancers. In our survey of the printed work, 25–52% of primary oral squamous – cell carcinomas had alkyl MGMT. On chromosome 10q26, O6 – methylguanine – DNA methyltransferase gene is located, which encodes MGMT, a DNA repair enzyme that eliminate O6 guanine DNA adducts caused by alkylating agents. CpG island hypermethylation of the MGMT promoter region results in gene silencing with loss of MGMT repair capacity which is thought to drive cancer progression. Epigenetic silencing of MGMT has been associated with OSCCs where tobacco exposure and betel quid chewing are suspected to be etiological factors.[ Huang SH et.al(2010)]
How it works
Secreted Apoptosis-Related macromolecule (SARP) families square measure thought-about to counteract the oncogenic Wnt sign pathway, and inactivation of this factor could aid cancer development and progression. SARP proteins, additionally named sFRP (for Secreted Frizzled-Related Protein), exert differential effects on osteoblastic differentiation of mouse mesenchymal cells and cellular programmed cell death of mouse osteoblasts in vitro[Cho, S.W et.al(2008)]. SARP2 methylation was determined in each begnin and malignant tumors and no applied mathematics link can be found between SARP2 methylation and illness progression.
Survivin is another important factor that modifies apoptotic processes in oral cancer and in other different types of cancer found in our body by modulating cell cycle, gratifying the overpowering of checkpoints. It has been recorded that the transcription of this gene rises in various tumour samples like in those that have been taken from the patients suffering from oral cancer and it has been found that it was also connected with clinical as well as pathological features ; in addition this gene’s expression is absent in normal tissue[Lo Muzio, L et.al(2003), Khan, Z et.al(2009)]. Single nucleotide polymorphism was also correlated wth the increased expression of survivn gene in the basic cancer research. Although there have been facts that suggest that hypomethylation[Gasche, J.A et.al(2012), Chen, Y.K et.al (2005), Hsue, S.S et.al (2008)] is found in this gene contradictory to normal samples where hypermethylation averts the overexpression.
DAPK1 stands for death associated protein kinase 1 involved in OSCC as one of the hypermethylated apoptotic gene that could serve as a biomarker in future. The location is found on gene locus 9q34.1. It is responsible for operating serine/threonine kinase pathway that initiates apoptosis by calcium/calmodulin (i.e.,proapoptotic)[Kulkarni, V et.al(2004), Kato, K et.al(2006), Ha, P.K el.al(2006)]. It was found from few reports that 18-27% of promoter hypermethylation was observed in DAP[(Hasegawa, M et.al(2002), Sanchez-Cespedes, M et.al(2000), Rosas, S.L et.al (2001)]. Both Intrinsic and Extrinsic type of apoptosis can be performed by DAPK. In various cancers the hypermethylation of DAPK purely indicates its correlation with disease. Methylation is responsible for the reduced gene expression of DAPK gene and also the blocked apoptosis process indicates that the initiation of tumour begins and another events at molecular level also described.[Mittag, F et.al(2006)]
P53 (TP53) is a tumour suppressor protein located on 17p13.1. This gene plays a very vital role in several processes such as cellular differentiation, cell cycle progression, DNA repair and apoptosis. If any unfavourable changes occur either due to any external or internal factors it results into rise of p53 expression that ultimately chokes cellular functions, permitting DNA repair. It has been observed that in most types of cancers, the mutation in p53 is found involving OSCC. The methylation status of p53 is approx 25% to 69%[ Levine, A.J et.al(1991), Boyle, J.O et.al (1998), Caamano, J et.al (1993), Baral, R(1998)]. Epigentic changes also led the reduced activity of p53. Therefore epigenetic silencing of p53 protein (non mutated) due to HPV virus , mainly involving HPV 16 and 18 found in OSCC like in few laryngeal cancers.
XAF-1 gene codes for the pro-apoptotic protein XIAP-associated Factor 1 which is found on gene locus 17p13.1. it indicates progression in P53 apoptotic pathway in Previously the methylation of this gene has encountred in various types of cancers such as Bladder , Oesophageal , colon , lung , colorectal etc. The region that has been found closely associated with XAF-1gene is around +236 – 196 bp upstream of the transcription site was proven to be indicative of a loss of XAF1 expression in panel of 16 HGG cell lines.
APAF-1 which is one of the apoptotic gene gets inactive in skin cancer (malignant), melanomas silencing and is partly due to Loss Of Heterozygosity(LOH). The drug that has been used for treatment i.e., 5-aza has contrary risen the gene expression in methylated melanomas or leukemia cells but the relation between gene methylation and silencing haven’t discussed yet and possibilities could be based on tissue. [Soengas, M.S et.al(2001)].