DNA methylation markers of surfactant proteins in lung cancer

Zhenwu Lin, Neal J. Thomas, Marina Bibikova, Carola Seifart, Yunhua Wang, Xiaoxuan Guo, Guirong Wang, Ekkehard Vollmer, Torsten Goldmann, Eliza Wickham Garcia, Lixin Zhou, Jian Bing Fan, Joanna Floros

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)181-191
Number of pages11
JournalInternational journal of oncology
Volume31
Issue number1
StatePublished - Jul 1 2007

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DNA Methylation
Genetic Markers
Surface-Active Agents
Pulmonary Surfactant-Associated Protein D
Lung Neoplasms
Proteins
Methylation
Squamous Cell Carcinoma
Adenocarcinoma
Lung
DNA Fingerprinting
Innate Immunity
Neoplasms
Biomarkers
Inflammation
Gene Expression
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Lin, Zhenwu ; Thomas, Neal J. ; Bibikova, Marina ; Seifart, Carola ; Wang, Yunhua ; Guo, Xiaoxuan ; Wang, Guirong ; Vollmer, Ekkehard ; Goldmann, Torsten ; Garcia, Eliza Wickham ; Zhou, Lixin ; Fan, Jian Bing ; Floros, Joanna. / DNA methylation markers of surfactant proteins in lung cancer. In: International journal of oncology. 2007 ; Vol. 31, No. 1. pp. 181-191.
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abstract = "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.",
author = "Zhenwu Lin and Thomas, {Neal J.} and Marina Bibikova and Carola Seifart and Yunhua Wang and Xiaoxuan Guo and Guirong Wang and Ekkehard Vollmer and Torsten Goldmann and Garcia, {Eliza Wickham} and Lixin Zhou and Fan, {Jian Bing} and Joanna Floros",
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Lin, Z, Thomas, NJ, Bibikova, M, Seifart, C, Wang, Y, Guo, X, Wang, G, Vollmer, E, Goldmann, T, Garcia, EW, Zhou, L, Fan, JB & Floros, J 2007, 'DNA methylation markers of surfactant proteins in lung cancer', International journal of oncology, vol. 31, no. 1, pp. 181-191.

DNA methylation markers of surfactant proteins in lung cancer. / Lin, Zhenwu; Thomas, Neal J.; Bibikova, Marina; Seifart, Carola; Wang, Yunhua; Guo, Xiaoxuan; Wang, Guirong; Vollmer, Ekkehard; Goldmann, Torsten; Garcia, Eliza Wickham; Zhou, Lixin; Fan, Jian Bing; Floros, Joanna.

In: International journal of oncology, Vol. 31, No. 1, 01.07.2007, p. 181-191.

Research output: Contribution to journalArticle

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AU - Lin, Zhenwu

AU - Thomas, Neal J.

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AU - Wang, Yunhua

AU - Guo, Xiaoxuan

AU - Wang, Guirong

AU - Vollmer, Ekkehard

AU - Goldmann, Torsten

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AU - Fan, Jian Bing

AU - Floros, Joanna

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N2 - 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.

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Lin Z, Thomas NJ, Bibikova M, Seifart C, Wang Y, Guo X et al. DNA methylation markers of surfactant proteins in lung cancer. International journal of oncology. 2007 Jul 1;31(1):181-191.