Surfactant proteins play important roles in lung
surfactant function and innate immunity. The DNA methylation state of 11 CpG sites of
surfactant protein (SP)-A1, -B, -C, and -D was determined using universal bead arrays. A total of 90 cancerous and non-cancerous tissues from 23 patients with
adenocarcinoma and 22 with
squamous cell carcinoma were studied. These were divided into a training set and a testing set. The results indicate that DNA methylation profiling of these CpGs is associated with
lung cancer. Four CpG sites, SP-A1_370, SP-A1_1080,
SP-D_1170, and
SP-D_1370, were hypomethylated in
cancer and were significantly associated with both
adenocarcinoma and
squamous cell carcinoma, indicating that they have the potential to be used as
biomarkers for
lung cancer diagnosis and treatment. Normal lung tissues with a higher level of unmethylated SP-A1_1468 and
SP-D_1170 CpG exhibited a higher level of SP-A1 and
SP-D gene transcripts indicating that CpG methylation may play a role in gene expression. When the non-cancerous tissues were compared to cancerous tissues in patients with
adenocarcinoma, the methylation profile results of these 46 samples (23 cancerous and 23 non-cancerous) could be clustered into 4 groups by agglomerative nesting. The percentage of
tumor samples in each group was 0, 58, 91, and 100, respectively. A similar pattern was observed in
squamous cell carcinoma patients. We speculate that SP-A1 and
SP-D are subject to methylation/demethylation regulatory mechanisms and are involved in
lung cancer pathogenesis by virtue of their function in innate host defense and/or regulation of
inflammation.