Differential expression of RUNX genes in human esophageal squamous cell carcinoma: downregulation of RUNX3 worsens patient prognosis.
BACKGROUND
The RUNX proteins are a family of transcriptional factors that have essential functions during embryogenesis and development, whereas deregulation in expression of RUNXs is often linked to tumor formation. To date, there has been no study describing the precise expression, prognostic impact and methylation status of RUNXs in esophageal squamous cell carcinoma.


METHODS
Resected specimens from 61 patients with esophageal SCC were used to identify the expression of RUNX1, RUNX2 and RUNX3 by real-time RT-PCR. Localization of mRNA was done by in situ hybridization, expression of Smad4 was evaluated by immunohistochemistry, and the methylation status of RUNX3 was analyzed by methylation-specific PCR.


RESULTS
RUNX3 had a significant impact on patient prognosis with worse survival in the RUNX3-negative group. In early tumors (T1/T2), the prevalence of lymph vessel invasion and the number of metastatic lymph nodes were significantly higher in RUNX3-negative tumors. Furthermore, RUNX3 became a strong prognostic factor only in Smad4-positive tumors. Also, the methylation status of the RUNX3 promoter had a significant correlation with the loss of RUNX3 expression.


CONCLUSIONS
Downregulation of RUNX3 may play a role in disease progression of esophageal SCC, and hypermethylation of the promoter region might be one of the crucial pathways to silence RUNX3 gene.
Tonomoto
Yasuhito
Y
Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Izumo, Japan. yasuhito_tonomoto@yahoo.co.jp
Tachibana
Mitsuo
M
Dhar
Dipok Kumar
DK
Onoda
Toshinao
T
Hata
Kohkichi
K
Ohnuma
Hideyuki
H
Tanaka
Tsuneo
T
Nagasue
Naofumi
N
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D050657:Core Binding Factor alpha Subunits / Q000235:genetics*; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies
D050677:Core Binding Factor Alpha 3 Subunit; D050657:Core Binding Factor alpha Subunits; C493729:Runx3 protein, human