TY - JOUR
T1 - Clinical significance of MLH1 methylation and CpG island methylator phenotype as prognostic markers in patients with gastric cancer
AU - Shigeyasu, Kunitoshi
AU - Nagasaka, Takeshi
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
N1 - Publisher Copyright:
© 2015 Shigeyasu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/6/29
Y1 - 2015/6/29
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0130409
DO - 10.1371/journal.pone.0130409
M3 - Article
C2 - 26121593
AN - SCOPUS:84938633282
SN - 1932-6203
VL - 10
JO - PLoS One
JF - PLoS One
IS - 6
M1 - e0130409
ER -
