title: DNA methylation profile and expression of surfactant protein A2 gene in lung cancer.
abstract: Knowledge of the methylation profile of genes allow for the identification of biomarkers that may guide diagnosis and effective treatment of disease. Human surfactant protein A (SP-A) plays an important role in lung homeostasis and immunity, and is encoded by two genes (SFTPA1 and SFTPA2). The goal of this study was to identify differentially methylated CpG sites in the promoter region of the SFTPA2 gene in lung cancer tissue, and to determine the correlation between the promoter's methylation profile and gene expression. For this, we collected 28 pairs of cancerous human lung tissue and adjacent noncancerous (NC) lung tissue: 17 adenocarcinoma (AC), 9 squamous cell carcinoma (SCC), and 2 AC with SCC features, and we evaluated DNA methylation of the SFTPA2 promoter region by bisulfite conversion. Our results identified a higher methylation ratio in one CpG site of the SFTPA2 gene in cancerous tissue versus NC tissue (0.36 versus 0.11, p = 0.001). When assessing AC samples, we also found cancerous tissues associated with a higher methylation ratio (0.43 versus 0.10, p = 0.02). In the SCC group, although cancerous tissue showed a higher methylation ratio (0.22 versus 0.11), this difference was not statistically significant (p = 0.35). Expression of SFTPA2 mRNA and total SP-A protein was significantly lower in cancer tissue when compared to adjacent NC tissue (p < 0.001), and correlated with the hypermethylated status of an SFTPA2 CpG site in AC samples. The findings of this pilot study may hold promise for future use of SFTPA2 as a biomarker for the diagnosis of lung cancer.
authors.affiliation: 1Pediatric Critical Care Division, Department of Pediatrics, Pennsylvania State Children's Hospital, The Pennsylvania State University College of Medicine , Hershey, PA , United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Grageda
authors.forename: Patricia
authors.initials: P
authors.lastname: Silveyra
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Thomas
authors.forename: Susan L
authors.initials: SL
authors.lastname: DiAngelo
authors.forename: Joanna
authors.initials: J
authors.lastname: Floros
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D010865:Pilot Projects; D011401:Promoter Regions, Genetic / Q000235:genetics; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D037662:Pulmonary Surfactant-Associated Protein A; D012333:RNA, Messenger; C445843:SFTPA2 protein, human
keywords: SP-A; adenocarcinoma; methylation; squamous cell carcinoma