The aim of this study was to explore the association of CpG islands methylation of liver kinase B1 (LKB1) with primary lung cancer and smoking, providing a theoretical basis for the demethylating drug to treat lung cancer by detecting the LKB1 promoter CpG methylation. mRNA expression of LKB1 were detected by in situ hybridization and methylation status on Hap II locus of the promoter of LKB1 was analyzed by methylation-specific polymerase chain reaction (PCR). 7 of 80 LKB1 positive cases had methylation on CpG islands while 18 of 44 LKB1 negative cases had methylation on CpG islands. The difference was significant between CpG island methylation and LKB1 expression. 8 of 54 cases of early and middle lung cancer were detected LKB1 promoter CpG island methylation while 30 controls were not detected, the difference was significant. 5 of 64 more-than-5-year cases had methylation on CpG islands while 20 of 60 less-than-5-year cases had methylation. The difference was significant between of 5-year survival and CpG island methylation of LKB1. 22 of 74 smoking cases of lung cancer had methylation on CpG islands of LKB1 while only 3 of 50 non-smoking cases had methylation. The difference of smoking and CpG island methylation of LKB1 was significant. LKB1 promoter CpG islands aberrant methylation is closely associated with the occurrence, development and prognosis of lung cancer, especially with smoking history including clinical early diagnosis and prognosis. CpG islands methylation in the promoter of LKB1 is likely important one of the mechanism of smoking-associated lung cancer.
Keywords: Liver kinase B1; lung cancer; methylation; methylation specific PCR; smoking.