Site-specific Hypermethylation of RUNX3 Predicts Poor Prognosis in Gastric Cancer.
Methylation status of RUNX3 remains largely unknown in gastric cancer (GC). The aim of this study was to prognostically evaluate the methylation level of CpG sites within RUNX3 promoter region in GC.



Using pyrosequencing, we quantitatively explored the methylation status of 8 CpG sites within RUNX3 promoter region for 76 gastric cancer and 24 normal gastric tissues. We then analyzed the association between methylation level of each CpG site and clinicopathological characteristics and outcomes in the cohort.



Methylation of RUNX3 promoter was significantly higher in GC than normal subjects. Overall methylation level was closely associated with tumor invasion and TNM stage. Positive associations were found between hypermethylation of the following concerned sites and variables: site -1392, -1397, -1403, -1415 and tumor invasion, as well as TNM stage; site -1392 and lymph node metastasis along with number of lymph node metastases; site -1415 and cancer recurrence; site -1403, -1415 and cancer-related deaths. In multivariate analysis, tumor invasion was correlated with sites -1392 and -1397. Lymph node metastasis was associated with site -1392. Most importantly, methylation of site -1415 was associated with poor survival by using Cox survival regression.



Analysis of RUNX3 gene promoter by quantitative pyrosequencing suggested methylation status of RUNX3 is different in normal and tumor tissues. RUNX3 methylation level is associated with GC, especially the methylation at site -1415 contributes to the poor prognosis in GC. Thus, RUNX3 methylation may serve as a valuable diagnostic and prognostic biomarker in GC.
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Na
N
Wang
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Fang
F
Sui
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Jingjing
J
Ma
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Xi
X
Su
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Jiazhe
J
Liu
Department of Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Demao
D
Yao
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Bingyin
B
Shi
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Peng
P
Hou
Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China. Electronic address: yangqi2015@mail.xjtu.edu.cn.
Qi
Q
Yang
D000368:Aged; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
D050677:Core Binding Factor Alpha 3 Subunit
Gastric cancer; Gene methylation; Prognostic value; Runt-related transcription factor 3 (RUNX3)