PURPOSE: To identify the
DNA methylation biomarkers for the detection of the stage I non-small cell
lung cancer (
NSCLC). MATERIALS AND METHODS: The
methylated state of p16INK4A,
ESR1, HOX9, RASSF1A,
DAPK1, PTEN,
ABCB1, MGMT, APC and
MT1G genes that have been reported frequently
methylated in
lung cancer was determined using methylation-specific
PCR in four
lung cancer cell lines, 124 cancer tissues of the stage I
NSCLC and 26 non-cancerous disease tissues. RESULT: The RASSF1A (53/124, 42.74%), APC (49/123, 39.52%),
ESR1 (37/124, 29.84%),
ABCB1 (31/124, 24.19%,
MT1G (25/124, 20.16%) and
HOXC9 (17/124, 13.71%) genes were more frequently
methylated in the
lung tissue from the stage I
NSCLC than the non-cancerous
lesion patients (2/26, 7.69%, P < 0.01; 2/26, 7.69%, P < 0.01; 2/26, 7.69%, P < 0.05; 1/26, 3.85% P < 0.01; 0/26 0%,
P value: <0.01; 0/26, 0%, P < 0.05, respectively). p16INK4A was
methylated in 28/124 (22.56%) of cancer tissues and 2/26 (7.69%) of non-cancerous tissues (
P value >0.05). No significant association between the
methylated state of the genes and the
smoking, age or the pathologic types (
squamous carcinoma,
adenoma and the mixed types) was found. However, p16INK4A
methylation was more frequently detected in the male (23/80, 28.75%) than the female (5/44, 11.36%, P > 0.05) patients. MGMT was barely
methylated: 1/67, 1.49%), while
DAPK1 and PTEN were not at all
methylated in the cancer groups. CONCLUSIONS:
Methylation analysis in tissue of RASSF1A, APC,
ESR1,
ABCB1 and
HOXC9 genes confirmed 79.8% of the existing diagnosis for the stage I
NSCLC at specificity: 73.1%. The insufficiency of predicting disease onset in China, using the previously recommended targets (MGMT,
DAPK1 and PTEN) in the United States reflects a potential disease disparity between these two populations. Alternatively,
methylated state of this set of genes may be more specific to the late rather than the early stage of
NSCLC.
