Clinical significance of MLH1 methylation and CpG island methylator phenotype as prognostic markers in patients with gastric cancer

Kunitoshi Shigeyasu, Takeshi Nagasaka, Yoshiko Mori, Naosuke Yokomichi, Takashi Kawai, Tomokazu Fuji, Keisuke Kimura, Yuzo Umeda, Shunsuke Kagawa, Ajay Goel, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

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Abstract

Background: To improve the outcome of patients suffering from gastric cancer, a better understanding of underlying genetic and epigenetic events in this malignancy is required. Although CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) have been shown to play pivotal roles in gastric cancer pathogenesis, the clinical significance of these events on survival outcomes in patients with gastric cancer remains unknown. Methods: This study included a patient cohort with pathologically confirmed gastric cancer who had surgical resections. A cohort of 68 gastric cancers was analyzed. CIMP and MSI statuses were determined by analyzing promoter CpG island methylation status of 28 genes/loci, and genomic instability at 10 microsatellite markers, respectively. A Cox's proportional hazards model was performed for multivariate analysis including age, stage, tumor differentiation, KRAS mutation status, and combined CIMP/MLH1methylation status in relation to overall survival (OS). Results: By multivariate analysis, longer OS was significantly correlated with lower pathologic stage (P = 0.0088), better tumor differentiation (P = 0.0267) and CIMP-high and MLH1 3′ methylated status (P = 0.0312). Stratification of CIMP status with regards to MLH1 methylation status further enabled prediction of gastric cancer prognosis. Conclusions: CIMP and/or MLH1 methylation status may have a potential to be prognostic biomarkers for patients with gastric cancer.

Original languageEnglish
Article numbere0130409
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 29 2015

Fingerprint

CpG Islands
Methylation
stomach neoplasms
methylation
Stomach Neoplasms
Phenotype
phenotype
Microsatellite Repeats
Microsatellite Instability
microsatellite repeats
multivariate analysis
Survival
Tumors
Multivariate Analysis
Neoplasms
neoplasms
Genomic Instability
Biomarkers
resection
Proportional Hazards Models

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Clinical significance of MLH1 methylation and CpG island methylator phenotype as prognostic markers in patients with gastric cancer. / Shigeyasu, Kunitoshi; Nagasaka, Takeshi; Mori, Yoshiko; Yokomichi, Naosuke; Kawai, Takashi; Fuji, Tomokazu; Kimura, Keisuke; Umeda, Yuzo; Kagawa, Shunsuke; Goel, Ajay; Fujiwara, Toshiyoshi.

In: PLoS One, Vol. 10, No. 6, e0130409, 29.06.2015.

Research output: Contribution to journalArticle

Shigeyasu, Kunitoshi ; Nagasaka, Takeshi ; Mori, Yoshiko ; Yokomichi, Naosuke ; Kawai, Takashi ; Fuji, Tomokazu ; Kimura, Keisuke ; Umeda, Yuzo ; Kagawa, Shunsuke ; Goel, Ajay ; Fujiwara, Toshiyoshi. / Clinical significance of MLH1 methylation and CpG island methylator phenotype as prognostic markers in patients with gastric cancer. In: PLoS One. 2015 ; Vol. 10, No. 6.
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AU - Mori, Yoshiko

AU - Yokomichi, Naosuke

AU - Kawai, Takashi

AU - Fuji, Tomokazu

AU - Kimura, Keisuke

AU - Umeda, Yuzo

AU - Kagawa, Shunsuke

AU - Goel, Ajay

AU - Fujiwara, Toshiyoshi

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