A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically resected stage i to IIIA non-small-cell lung cancers

Alexander Drilon, Hirofumi Sugita, Camelia S. Sima, Marjorie Zauderer, Charles M. Rudin, Mark G. Kris, Valerie W. Rusch, Christopher G. Azzoli

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene promoter methylation in early-stage non-small-cell lung cancers (NSCLCs), few studies have investigated this question prospectively. METHODS: Primary tumor tissue from patients with resected pathologic stage I to IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual tumor suppressor genes (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. RESULTS: A total of 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage I disease (62%). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS (p = 0.03). The total number of genes with methylated promoters did not correlate with RFS (p = 0.89) or OS (p = 0.55). CONCLUSION: Contrary to data established by previous retrospective series, tumor suppressor gene promoter methylation (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs.

Original languageEnglish (US)
Pages (from-to)1272-1277
Number of pages6
JournalJournal of Thoracic Oncology
Volume9
Issue number9
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Tumor Suppressor Genes
Non-Small Cell Lung Carcinoma
Methylation
Biomarkers
Prospective Studies
Survival
Recurrence
Neoplasms
p16 Genes
Reverse Transcriptase Polymerase Chain Reaction
Genes

Keywords

  • Epigenetics
  • Non-small-cell lung cancer
  • Promoter methylation
  • Resected
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Medicine(all)

Cite this

A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically resected stage i to IIIA non-small-cell lung cancers. / Drilon, Alexander; Sugita, Hirofumi; Sima, Camelia S.; Zauderer, Marjorie; Rudin, Charles M.; Kris, Mark G.; Rusch, Valerie W.; Azzoli, Christopher G.

In: Journal of Thoracic Oncology, Vol. 9, No. 9, 2014, p. 1272-1277.

Research output: Contribution to journalArticle

Drilon, Alexander ; Sugita, Hirofumi ; Sima, Camelia S. ; Zauderer, Marjorie ; Rudin, Charles M. ; Kris, Mark G. ; Rusch, Valerie W. ; Azzoli, Christopher G. / A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically resected stage i to IIIA non-small-cell lung cancers. In: Journal of Thoracic Oncology. 2014 ; Vol. 9, No. 9. pp. 1272-1277.
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abstract = "INTRODUCTION: While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene promoter methylation in early-stage non-small-cell lung cancers (NSCLCs), few studies have investigated this question prospectively. METHODS: Primary tumor tissue from patients with resected pathologic stage I to IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual tumor suppressor genes (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. RESULTS: A total of 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88{\%}) with lung adenocarcinoma (78{\%}) and pathologic stage I disease (62{\%}). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS (p = 0.03). The total number of genes with methylated promoters did not correlate with RFS (p = 0.89) or OS (p = 0.55). CONCLUSION: Contrary to data established by previous retrospective series, tumor suppressor gene promoter methylation (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs.",
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T1 - A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically resected stage i to IIIA non-small-cell lung cancers

AU - Drilon, Alexander

AU - Sugita, Hirofumi

AU - Sima, Camelia S.

AU - Zauderer, Marjorie

AU - Rudin, Charles M.

AU - Kris, Mark G.

AU - Rusch, Valerie W.

AU - Azzoli, Christopher G.

PY - 2014

Y1 - 2014

N2 - INTRODUCTION: While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene promoter methylation in early-stage non-small-cell lung cancers (NSCLCs), few studies have investigated this question prospectively. METHODS: Primary tumor tissue from patients with resected pathologic stage I to IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual tumor suppressor genes (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. RESULTS: A total of 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage I disease (62%). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS (p = 0.03). The total number of genes with methylated promoters did not correlate with RFS (p = 0.89) or OS (p = 0.55). CONCLUSION: Contrary to data established by previous retrospective series, tumor suppressor gene promoter methylation (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs.

AB - INTRODUCTION: While retrospective analyses support an association between early tumor recurrence and tumor suppressor gene promoter methylation in early-stage non-small-cell lung cancers (NSCLCs), few studies have investigated this question prospectively. METHODS: Primary tumor tissue from patients with resected pathologic stage I to IIIA NSCLCs was collected at the time of surgery and analyzed for promoter methylation via methylation-specific reverse transcriptase polymerase chain reaction (MethyLight). The primary objective was to determine an association between promoter methylation of 10 individual tumor suppressor genes (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, SOCS3, and ADAMTS8) and recurrence-free survival (RFS), with the secondary objectives of determining association with overall survival (OS), and relation to clinical or pathologic features. RESULTS: A total of 107 patients had sufficient tumor tissue for successful promoter methylation analysis. Majority of patients were former/current smokers (88%) with lung adenocarcinoma (78%) and pathologic stage I disease (62%). Median follow-up was 4 years. When controlled for pathologic stage, promoter methylation of the individual genes CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8 was not associated with RFS. Promoter methylation of the same genes was not associated with OS except for DAPK1 which was associated with improved OS (p = 0.03). The total number of genes with methylated promoters did not correlate with RFS (p = 0.89) or OS (p = 0.55). CONCLUSION: Contrary to data established by previous retrospective series, tumor suppressor gene promoter methylation (CDKN2A, CDH13, RASSF1, APC, MGMT, GSTP1, DAPK1, WIF1, and ADAMTS8) was not prognostic for early tumor recurrence in this prospective study of resected NSCLCs.

KW - Epigenetics

KW - Non-small-cell lung cancer

KW - Promoter methylation

KW - Resected

KW - Tumor suppressor gene

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