Abstract
Background: LATS1 (Large Tumor Suppressor, isoform 1) is a gene that forms a complex with the cyclin-dependent kinase, CDK1, and regulates cell cycle progression. Genetic modifications lead to a loss in the activity of LATS1 gene. OSCC is the most commonly emerging cancer caused by genetic as well as epigenetic changes. Epigenetics changes vary from one population to another because these are influenced by dietary factors and environmental factors. Tobacco chewing and smoking has been reported as major risk factors in OSCC. No report was found in the previous literature showing promoter hypermethylation of LATS1 gene. Methods:A total of 50 OSCC patients and 20 normal individuals were recruited in this study. Blood samples (50) from OSCC patients and blood samples (20) from healthy individuals as controls were used in the present study. Isolation of genomic DNA was carried out from blood using the standard phenol-chloroform extraction. Further Isolated DNA was modified with sodium bisulfite using the agarose bead method and finally, the methylation studies of LATS1 gene were carried out using Methylation-Specific PCR (MSP-PCR). Results:19 out of 50 patients (38.0%) were found to be methylated for LATS1 gene.; a statistically significant result was obtained (p -value= < 0.05) with an odds ratio of 0.37 in cases compared to controls. The status of methylation of LATS1 genes was also found to be statistically significantly associated with smokers and tobacco chewers (p-value = < 0.05). The methylation of LATS1 gene showed a significant risk of developing OSCC in patients. Conclusion:These results suggest that the LATS1 gene may provide a better alternative as a diagnostic biomarker. This is the first report on the promoter hypermethylation of LATS1 gene in OSCC patients among the North Indian population.
Highlights
Cancer is the most common, vicious, and dangerously increasing diseases of the world today, associated with high morbidity and mortality
Status of promoter hypermethylation Hypermethylation of Large Tumor Suppressor gene 1 (LATS1) was observed in 38% of Oral Squamous Cell Carcinoma (OSCC) patients. 19 out of 50 samples were found to be promoter hypermethylated through MSP (Methylation Specific PCR) in OSCC patients (Figure 2)
Hypermethylation of the LATS1 gene was observed in Serum samples, the intensity of MSB was found to be less in serum samples (Figure 4)
Summary
Cancer is the most common, vicious, and dangerously increasing diseases of the world today, associated with high morbidity and mortality. DNA methylation was the earliest epigenetic changes to be seen in cancer cells. It plays a significant role within the regulation of the Gene expression and chromatin design by providing a stable Gene silencing mechanism (Mahmood and Rabbani, 2019). The DNA methylation markers can be used in cancer diagnostics for both disease classification and detection because epigenetic changes occur very. The methylation of LATS1 gene showed a significant risk of developing OSCC in patients. Conclusion: These results suggest that the LATS1 gene may provide a better alternative as a diagnostic biomarker This is the first report on the promoter hypermethylation of LATS1 gene in OSCC patients among the North Indian population
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