Hypermethylation of FHIT as a Prognostic Marker in Nonsmall Cell Lung Carcinoma

Riichiroh Maruyama, Kenji Sugio, Ichiro Yoshino, Yoshihiko Maehara, Adi F. Gazdar

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

BACKGROUND. Methylation of CpG islands in the promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of the current study was to determine the correlation between the aberrant promoter methylation of multiple genes and survival in patients with nonsmall cell lung carcinoma (NSCLC). METHODS. The methylation status of nine genes was determined in 124 surgically resected NSCLC cases using methylation-specific polymerase chain reaction. RESULTS. The methylation frequencies of the genes tested in NSCLC specimens were 52% for E-cadherin (CDH1), 41% for RAS association domain family protein (RASSF1A), 38% for fragile histidine triad (FHIT) and adenomatous polyposis coli (APC), 27% for retinoic acid receptor beta (RARβ) and H-cadherin (CDH13), 20% for p16INK4A, 0.8% for O6-methylguanine-DNA-methyltransferase (MGMT), and 0% for glutathione S-transferase P1 (GSTP1). The survival of the patients with FHIT methylation-positive tumors was found to be significantly shorter than that for those patients with methylation-negative tumors (P = 0.03), even in those patients with International Union Against Cancer TNM Stage I or Stage II disease (P = 0.007). In contrast, there were no significant survival differences noted between the methylation-positive and methylation-negative tumors for the other genes tested. In addition, based on multivariate analyses, FHIT methylation-positive status was found to be independently associated with poor survival (P = 0.046) and disease stage (P < 0.0001). CONCLUSIONS. The results of the current study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC.

Original languageEnglish
Pages (from-to)1472-1477
Number of pages6
JournalCancer
Volume100
Issue number7
DOIs
Publication statusPublished - Apr 1 2004

Fingerprint

Histidine
Methylation
Carcinoma
Lung
Survival
Genes
Neoplasms
CpG Islands
Adenomatous Polyposis Coli
Methyltransferases
Cadherins
Glutathione Transferase
Tumor Suppressor Genes
Gene Frequency
Multivariate Analysis
Biomarkers
Polymerase Chain Reaction
DNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Maruyama, R., Sugio, K., Yoshino, I., Maehara, Y., & Gazdar, A. F. (2004). Hypermethylation of FHIT as a Prognostic Marker in Nonsmall Cell Lung Carcinoma. Cancer, 100(7), 1472-1477. https://doi.org/10.1002/cncr.20144

Hypermethylation of FHIT as a Prognostic Marker in Nonsmall Cell Lung Carcinoma. / Maruyama, Riichiroh; Sugio, Kenji; Yoshino, Ichiro; Maehara, Yoshihiko; Gazdar, Adi F.

In: Cancer, Vol. 100, No. 7, 01.04.2004, p. 1472-1477.

Research output: Contribution to journalArticle

Maruyama, R, Sugio, K, Yoshino, I, Maehara, Y & Gazdar, AF 2004, 'Hypermethylation of FHIT as a Prognostic Marker in Nonsmall Cell Lung Carcinoma', Cancer, vol. 100, no. 7, pp. 1472-1477. https://doi.org/10.1002/cncr.20144
Maruyama R, Sugio K, Yoshino I, Maehara Y, Gazdar AF. Hypermethylation of FHIT as a Prognostic Marker in Nonsmall Cell Lung Carcinoma. Cancer. 2004 Apr 1;100(7):1472-1477. https://doi.org/10.1002/cncr.20144
Maruyama, Riichiroh ; Sugio, Kenji ; Yoshino, Ichiro ; Maehara, Yoshihiko ; Gazdar, Adi F. / Hypermethylation of FHIT as a Prognostic Marker in Nonsmall Cell Lung Carcinoma. In: Cancer. 2004 ; Vol. 100, No. 7. pp. 1472-1477.
@article{4fa825a2f5a942cb8731adb33a9672f6,
title = "Hypermethylation of FHIT as a Prognostic Marker in Nonsmall Cell Lung Carcinoma",
abstract = "BACKGROUND. Methylation of CpG islands in the promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of the current study was to determine the correlation between the aberrant promoter methylation of multiple genes and survival in patients with nonsmall cell lung carcinoma (NSCLC). METHODS. The methylation status of nine genes was determined in 124 surgically resected NSCLC cases using methylation-specific polymerase chain reaction. RESULTS. The methylation frequencies of the genes tested in NSCLC specimens were 52{\%} for E-cadherin (CDH1), 41{\%} for RAS association domain family protein (RASSF1A), 38{\%} for fragile histidine triad (FHIT) and adenomatous polyposis coli (APC), 27{\%} for retinoic acid receptor beta (RARβ) and H-cadherin (CDH13), 20{\%} for p16INK4A, 0.8{\%} for O6-methylguanine-DNA-methyltransferase (MGMT), and 0{\%} for glutathione S-transferase P1 (GSTP1). The survival of the patients with FHIT methylation-positive tumors was found to be significantly shorter than that for those patients with methylation-negative tumors (P = 0.03), even in those patients with International Union Against Cancer TNM Stage I or Stage II disease (P = 0.007). In contrast, there were no significant survival differences noted between the methylation-positive and methylation-negative tumors for the other genes tested. In addition, based on multivariate analyses, FHIT methylation-positive status was found to be independently associated with poor survival (P = 0.046) and disease stage (P < 0.0001). CONCLUSIONS. The results of the current study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC.",
author = "Riichiroh Maruyama and Kenji Sugio and Ichiro Yoshino and Yoshihiko Maehara and Gazdar, {Adi F.}",
year = "2004",
month = "4",
day = "1",
doi = "10.1002/cncr.20144",
language = "English",
volume = "100",
pages = "1472--1477",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

TY - JOUR

T1 - Hypermethylation of FHIT as a Prognostic Marker in Nonsmall Cell Lung Carcinoma

AU - Maruyama, Riichiroh

AU - Sugio, Kenji

AU - Yoshino, Ichiro

AU - Maehara, Yoshihiko

AU - Gazdar, Adi F.

PY - 2004/4/1

Y1 - 2004/4/1

N2 - BACKGROUND. Methylation of CpG islands in the promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of the current study was to determine the correlation between the aberrant promoter methylation of multiple genes and survival in patients with nonsmall cell lung carcinoma (NSCLC). METHODS. The methylation status of nine genes was determined in 124 surgically resected NSCLC cases using methylation-specific polymerase chain reaction. RESULTS. The methylation frequencies of the genes tested in NSCLC specimens were 52% for E-cadherin (CDH1), 41% for RAS association domain family protein (RASSF1A), 38% for fragile histidine triad (FHIT) and adenomatous polyposis coli (APC), 27% for retinoic acid receptor beta (RARβ) and H-cadherin (CDH13), 20% for p16INK4A, 0.8% for O6-methylguanine-DNA-methyltransferase (MGMT), and 0% for glutathione S-transferase P1 (GSTP1). The survival of the patients with FHIT methylation-positive tumors was found to be significantly shorter than that for those patients with methylation-negative tumors (P = 0.03), even in those patients with International Union Against Cancer TNM Stage I or Stage II disease (P = 0.007). In contrast, there were no significant survival differences noted between the methylation-positive and methylation-negative tumors for the other genes tested. In addition, based on multivariate analyses, FHIT methylation-positive status was found to be independently associated with poor survival (P = 0.046) and disease stage (P < 0.0001). CONCLUSIONS. The results of the current study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC.

AB - BACKGROUND. Methylation of CpG islands in the promoter and upstream coding regions has been identified as a mechanism for transcriptional inactivation of tumor suppressor genes. The purpose of the current study was to determine the correlation between the aberrant promoter methylation of multiple genes and survival in patients with nonsmall cell lung carcinoma (NSCLC). METHODS. The methylation status of nine genes was determined in 124 surgically resected NSCLC cases using methylation-specific polymerase chain reaction. RESULTS. The methylation frequencies of the genes tested in NSCLC specimens were 52% for E-cadherin (CDH1), 41% for RAS association domain family protein (RASSF1A), 38% for fragile histidine triad (FHIT) and adenomatous polyposis coli (APC), 27% for retinoic acid receptor beta (RARβ) and H-cadherin (CDH13), 20% for p16INK4A, 0.8% for O6-methylguanine-DNA-methyltransferase (MGMT), and 0% for glutathione S-transferase P1 (GSTP1). The survival of the patients with FHIT methylation-positive tumors was found to be significantly shorter than that for those patients with methylation-negative tumors (P = 0.03), even in those patients with International Union Against Cancer TNM Stage I or Stage II disease (P = 0.007). In contrast, there were no significant survival differences noted between the methylation-positive and methylation-negative tumors for the other genes tested. In addition, based on multivariate analyses, FHIT methylation-positive status was found to be independently associated with poor survival (P = 0.046) and disease stage (P < 0.0001). CONCLUSIONS. The results of the current study suggest that methylation of FHIT is a useful biomarker of biologically aggressive disease in patients with NSCLC.

UR - http://www.scopus.com/inward/record.url?scp=1642400575&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1642400575&partnerID=8YFLogxK

U2 - 10.1002/cncr.20144

DO - 10.1002/cncr.20144

M3 - Article

C2 - 15042681

AN - SCOPUS:1642400575

VL - 100

SP - 1472

EP - 1477

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 7

ER -