DNA methylation profile and expression of surfactant protein A2 gene in lung cancer

Melissa Grageda, Patricia Silveyra, Neal J. Thomas, Susan L. Diangelo, Joanna Floros

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)93-102
Number of pages10
JournalExperimental Lung Research
Volume41
Issue number2
DOIs
StatePublished - Mar 1 2015

Fingerprint

DNA Methylation
varespladib methyl
Surface-Active Agents
Lung Neoplasms
Genes
Tissue
Methylation
Proteins
Adenocarcinoma
Pulmonary Surfactant-Associated Protein A
Squamous Cell Carcinoma
Biomarkers
Genetic Promoter Regions
Lung
Transcriptome
Gene expression
Immunity
Homeostasis
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

Cite this

Grageda, Melissa ; Silveyra, Patricia ; Thomas, Neal J. ; Diangelo, Susan L. ; Floros, Joanna. / DNA methylation profile and expression of surfactant protein A2 gene in lung cancer. In: Experimental Lung Research. 2015 ; Vol. 41, No. 2. pp. 93-102.
@article{86a044484ab141c88e0c34a7038cde57,
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.",
author = "Melissa Grageda and Patricia Silveyra and Thomas, {Neal J.} and Diangelo, {Susan L.} and Joanna Floros",
year = "2015",
month = "3",
day = "1",
doi = "10.3109/01902148.2014.976298",
language = "English (US)",
volume = "41",
pages = "93--102",
journal = "Experimental Lung Research",
issn = "0190-2148",
publisher = "Informa Healthcare",
number = "2",

}

DNA methylation profile and expression of surfactant protein A2 gene in lung cancer. / Grageda, Melissa; Silveyra, Patricia; Thomas, Neal J.; Diangelo, Susan L.; Floros, Joanna.

In: Experimental Lung Research, Vol. 41, No. 2, 01.03.2015, p. 93-102.

Research output: Contribution to journalArticle

TY - JOUR

T1 - DNA methylation profile and expression of surfactant protein A2 gene in lung cancer

AU - Grageda, Melissa

AU - Silveyra, Patricia

AU - Thomas, Neal J.

AU - Diangelo, Susan L.

AU - Floros, Joanna

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84923271015&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923271015&partnerID=8YFLogxK

U2 - 10.3109/01902148.2014.976298

DO - 10.3109/01902148.2014.976298

M3 - Article

C2 - 25514367

AN - SCOPUS:84923271015

VL - 41

SP - 93

EP - 102

JO - Experimental Lung Research

JF - Experimental Lung Research

SN - 0190-2148

IS - 2

ER -