Promoter hypermethylation of the p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers

Mitsuru Yoshino, Makoto Suzuki, Lei Tian, Yasumitsu Moriya, Hidehisa Hoshino, Tatsuro Okamoto, Shigetoshi Yoshida, Kiyoshi Shibuya, Ichiro Yoshino

Research output: Contribution to journalArticle

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Abstract

Hypermethylation of promoter CpG islands is a major inactivation mechanism of tumor suppressor genes, some of which are thought to be related to the prognosis of patients with non-small cell lung cancer (NSCLC). Therefore, hypermethylation of the specific genes may be expected to serve as a prognostic biomarker for NSCLC. In this study, the methylation status of 14 genes was analyzed in 44 stage IA NSCLC cases using methylation-specific PCR. Hypermethylation was detected in PTGER2 (70% of cases), DRM/Gremlin (66%), sFRP-2 (57%), IL-12Rβ2 (48%), Reprimo (41%), APC (39%), CXCL12 (39%), HPP1 (30%), SPARC (30%), sFRP-5 (30%), p16 (25%), RUNX3 (20%), sFRP-1 (20%) and Wif-1 (16%). Patients with p16, sFRP-5, Wif-1 or CXCL12 methylation had a significantly shorter duration of relapse-free survival than their counterparts with an unmethylated gene (p16, P=0.011; sFRP-5, P=0.030, Wif-1, P=0.036; CXCL12, P=0.026). Also, those with methylated HPP1, p16 or Wif-1 had a significantly shorter duration of overall survival (HPP1, P=0.031; p16, P=0.026; Wif-1, P=0.008). Multivariate analysis revealed that p16 methylation in relapse-free survival and Wif-1 methylation in overall survival were the strongest independent prognostic factors (p16, P=0.036; Wif-1, P=0.035). In conclusion, the hypermethylation of the p16 and Wif-1 genes has potential as biomarkers that may be used to predict the prognosis of stage IA NSCLC.

Original languageEnglish
Pages (from-to)1201-1209
Number of pages9
JournalInternational journal of oncology
Volume35
Issue number5
DOIs
Publication statusPublished - Nov 1 2009

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Non-Small Cell Lung Carcinoma
Methylation
Survival
Genes
Biomarkers
p16 Genes
Recurrence
CpG Islands
Tumor Suppressor Genes
Interleukin-2
Multivariate Analysis
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Promoter hypermethylation of the p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers. / Yoshino, Mitsuru; Suzuki, Makoto; Tian, Lei; Moriya, Yasumitsu; Hoshino, Hidehisa; Okamoto, Tatsuro; Yoshida, Shigetoshi; Shibuya, Kiyoshi; Yoshino, Ichiro.

In: International journal of oncology, Vol. 35, No. 5, 01.11.2009, p. 1201-1209.

Research output: Contribution to journalArticle

Yoshino, M, Suzuki, M, Tian, L, Moriya, Y, Hoshino, H, Okamoto, T, Yoshida, S, Shibuya, K & Yoshino, I 2009, 'Promoter hypermethylation of the p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers', International journal of oncology, vol. 35, no. 5, pp. 1201-1209. https://doi.org/10.3892/ijo-00000437
Yoshino, Mitsuru ; Suzuki, Makoto ; Tian, Lei ; Moriya, Yasumitsu ; Hoshino, Hidehisa ; Okamoto, Tatsuro ; Yoshida, Shigetoshi ; Shibuya, Kiyoshi ; Yoshino, Ichiro. / Promoter hypermethylation of the p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers. In: International journal of oncology. 2009 ; Vol. 35, No. 5. pp. 1201-1209.
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title = "Promoter hypermethylation of the p16 and Wif-1 genes as an independent prognostic marker in stage IA non-small cell lung cancers",
abstract = "Hypermethylation of promoter CpG islands is a major inactivation mechanism of tumor suppressor genes, some of which are thought to be related to the prognosis of patients with non-small cell lung cancer (NSCLC). Therefore, hypermethylation of the specific genes may be expected to serve as a prognostic biomarker for NSCLC. In this study, the methylation status of 14 genes was analyzed in 44 stage IA NSCLC cases using methylation-specific PCR. Hypermethylation was detected in PTGER2 (70{\%} of cases), DRM/Gremlin (66{\%}), sFRP-2 (57{\%}), IL-12Rβ2 (48{\%}), Reprimo (41{\%}), APC (39{\%}), CXCL12 (39{\%}), HPP1 (30{\%}), SPARC (30{\%}), sFRP-5 (30{\%}), p16 (25{\%}), RUNX3 (20{\%}), sFRP-1 (20{\%}) and Wif-1 (16{\%}). Patients with p16, sFRP-5, Wif-1 or CXCL12 methylation had a significantly shorter duration of relapse-free survival than their counterparts with an unmethylated gene (p16, P=0.011; sFRP-5, P=0.030, Wif-1, P=0.036; CXCL12, P=0.026). Also, those with methylated HPP1, p16 or Wif-1 had a significantly shorter duration of overall survival (HPP1, P=0.031; p16, P=0.026; Wif-1, P=0.008). Multivariate analysis revealed that p16 methylation in relapse-free survival and Wif-1 methylation in overall survival were the strongest independent prognostic factors (p16, P=0.036; Wif-1, P=0.035). In conclusion, the hypermethylation of the p16 and Wif-1 genes has potential as biomarkers that may be used to predict the prognosis of stage IA NSCLC.",
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AU - Suzuki, Makoto

AU - Tian, Lei

AU - Moriya, Yasumitsu

AU - Hoshino, Hidehisa

AU - Okamoto, Tatsuro

AU - Yoshida, Shigetoshi

AU - Shibuya, Kiyoshi

AU - Yoshino, Ichiro

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