SDR9C7 promotes lymph node metastases in patients with esophageal squamous cell carcinoma

PLoS One. 2013;8(1):e52184. doi: 10.1371/journal.pone.0052184. Epub 2013 Jan 14.

Abstract

Background: The major reason for the poor prognosis of esophageal squamous cell carcinoma (ESCC) patients is lymph node (LN) metastases.

Methodology/principal: In the present study, gene expression profiling assay (GEP) was performed to identify the differences in gene expression profiles between primary ESCC tumors that were with LN metastases (N(+)) and those without LN metastases (N(-)).

Conclusions/significance: A total of 23 genes were identified as being significantly elevated, and 30 genes were sharply decreased in ESCC tumors that were N(+) compared with N- tumors. Among these genes, two transcripts of the short chain dehydrogenase/reductase family 9C, member 7 (SDR9C7) were observed 7 times more frequently in N(+) compared with N(-) tumors. Immunohistochemical staining showed that SDR9C7 expression closely correlated with metastasis, and would be a prognostic marker for ESCC patients. To investigate the role of SDR9C7 in the ESCC metastasis, repeated transwell assays were adopted to establish highly and non-invasive ESCC sublines, and western blot showed that SDR9C7 expression was markedly higher in highly invasive cells compared with non-invasive ones. Down-regulation of SDR9C7 dramatically inhibited the metastatic abilities in vitro and in vivo, and repressed the expression of MMP11 in highly invasive cells, indicating that SDR9C7 promotes ESCC metastasis partly through regulation of MMP11, and might be a potential prognostic and therapeutic marker for ESCC patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Animals
  • Blotting, Western
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Down-Regulation / genetics
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Lentivirus / metabolism
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology*
  • Male
  • Mice
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Up-Regulation / genetics

Substances

  • RNA, Messenger
  • RNA, Small Interfering
  • Oxidoreductases
  • SDR9C7 protein, human

Grants and funding

This work was supported in part by grants from the China Postdoctoral Science Foundation 20090461447, National Natural Science Foundations of China 81172288, and 81101689. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.