The application of molecular markers specific for lung cancer offers new possibilities for early detection. Recent evidence suggests that tumor cells may release DNA into the circulation, which is enriched in the serum and plasma. p16 tumor suppressor gene can be inactivated by promoter lesion methylation in many tumor types including lung cancer, We examined whether aberrant p16 methylation might also be found in the serum of patients with non-small cell lung cancer using real-time PCR.
Serum samples were obtained from 95 patients with non-small cell lung cancer, 66 adenocarcinomas, 23 squamous cell carcinomas, 6 large cell carcinomas and 32 normal controls. All patient were diagnosed at our hospital. We tested 127 samples to determine the quantity of p16 promoter methylation using real-time PCR.
Aberrant p16 promoter methylation of the tumor suppressor gene was detected in 25 of 95 NSCLC patients (mean:18.613±5.090), but only 2 of 32 normal control (mean: 1.258±0.871). There was a statistical difference between non small cell lung cancer patients and normal control (t-test: p<0.003). We drew the cutoff line at 3.0. Sensitivity was 26.3%, specificity was 93.8%, accuracy was 43.3%, positive predictive value was 92.6%. However there were no significant differences between p16 promoter methylation in serum and gender, smoking history, histological type and stage. Interestingly, we found a statistical difference about aging between less than 62 years old and over 63 years old in relation to p16 promoter methylation in serum of patient with non small cell lung cancer patients and normal control.(p=0.0088; Fisher’s exact test) Some cases were initially positive for methylated p16 DNA in serum before surgery, and all tuned negative after curative surgery.
There was a significant difference between non small cell lung cancer patients and normal control about the p16 methylation level.
Detection of aberrant p16 promoter rmethylation in serum using real time PCR appears useful for lung cancer diagnosis, early detection and clinical follow up.
Yasuhiro Suga, None.