High CpG island methylator phenotype is associated with lymph node metastasis and prognosis in gastric cancer.
Several studies have found that the promoter CpG island is frequently methylated in gastric cancer. The CpG island methylator phenotype (CIMP) defines concordant methylation of multiple promoter CpG island loci in a subset of gastric cancer. However, the relationship between CIMP and lymph node metastasis in gastric cancer is unknown. Our study aimed to characterize the role of CIMP in lymph node metastasis. Clinical specimens from 120 patients were analyzed and PCR was used to detect the methylation status of five genes (ALX4, TMEFF2, CHCHD10, IGFBP3, and NPR1). We measured the level of mRNA for the five genes by real-time RT-PCR. Microsatellite instability and Helicobacter pylori infection status were assayed by capillary electrophoresis and real-time PCR, respectively. DNA methylation in the five genes was correlated with low expression of the respective mRNA. With CIMP as the dependent variable, CIMP-high gastric cancer tended to show more distant lymph node metastasis, higher pathologic tumor classification, more pathologic metastasis, and higher pathologic TNM status. Microsatellite instability and H. pylori status were not significant predictors of prognosis. CIMP-high gastric cancer showed significantly worse survival compared with that of CIMP-low/CIMP-negative gastric cancer (P < 0.001). Our results show that there is an association between CIMP status and lymph node metastasis in gastric cancer and CIMP-high was an independent prognostic factor.
Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Hua-Yun
HY
Chen
Bao-He
BH
Zhu
Chang-Hua
CH
Zhang
Dong-Jie
DJ
Yang
Jian-Jun
JJ
Peng
Jian-Hui
JH
Chen
Fa-Keng
FK
Liu
Yu-Long
YL
He
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D016481:Helicobacter Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D016480:Helicobacter pylori / Q000235:genetics; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D053842:Microsatellite Instability; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D012334:RNA, Neoplasm; D060888:Real-Time Polymerase Chain Reaction; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000821:virology; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics
C416676:ALX4 protein, human; C554426:CHCHD10 protein, human; D004268:DNA-Binding Proteins; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C423567:TMEFF2 protein, human; D014157:Transcription Factors; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A