LRRTM1 gene methylation is a potential diagnostic and prognostic marker of pan-creatic cancer
Objective To investigate the epigenetic regulation of LRRTM1 gene expression and the possibility of LRRTM1 methylation as a diagnostic and prognostic marker.Methods LRRTM1 expression and promoter methylation status in 6 pancreatic cancer cell lines were detected by semi-quantitative RT-PCR and methylation-specific PCR(MSP).MSP was used to detect the methylation status of LRRTM1 in 101 cases of precancerous and 277 cases of pan-creatic cancer samples.Chi-square test was employed to analyze the association of LRRTM1 methylation and clinicopath-ological factors.Kaplan-Meier survival curves were plotted and Log-Rank test was used to compare overall survival.Uni-variate and multivariate Cox regression analyses were used to evaluate prognostic factors.Results The expression of LRRTM1 was lost in Capan1,Panc3.11,AsPC1 and PANC-28 cells,and the promoter region of LRRTM1 was com-pletely methylated in these cells.LRRTM1 was normally expressed in Capan2 and CFpac1 cells,and the promoter re-gion of LRRTM1 was unmethylated.The expression of LRRTM1 was restored in Capan1,Panc3.11,AsPC1 and PANC-28 cells,and unchanged in Capan2 and CFpac1 cells after 5-aza-dc treatment.These results indicated that the expression of LRRTM1 was regulated by promoter methylation in pancreatic cancer.It was further found that LRRTM1 was methylated in 16.83%(17/101)of precancerous samples and 52.35%(145/277)of primary pancreatic cancer,and the expression of LRRTM1 was associated with age(P<0.05).For 232 cases of pancreatic cancer patients with available survival data,LRRTM1 methylation was found to be significantly associated with poor overall survival(P<0.05).Conclusion LRRTM1 gene is frequently methylated in pancreatic cancer,and its expression is regulated by promoter methylation.LRRTM1 methylation is a potential diagnostic and prognostic marker for pancreatic cancer.
LRRTM1Pancreatic cancerDNA methylationMethylation specific PCR
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NSTL
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