Correlation between the high expression levels of cancer-germline genes with clinical characteristics in esophageal squamous cell carcinoma

Xinfeng Chen, Liping Wang, Dongli Yue, Jinyan Liu, Lan Huang, Li Yang, Ling Cao, Guohui Qin, Anqi Li, Dan Wang, Meng Wang, Yu Qi, Bin Zhang, Pierre van der Bruggen, Yi Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Antigens encoded by cancer-germline genes are attractive targets for cancer immunotherapy. In this study, we aimed to evaluate the mRNA expression of cancer-germline genes, expression of the encoded proteins in patients with esophageal squamous cell carcinoma (ESCC) and their correlations with clinical characteristics. In addition, the effects of downregulation cancer-germline genes on ESCC cells were assessed in vitro. Our results showed that cancer-germline genes were frequently expressed in ESCC samples. The positive rates of in ESCC samples were: 87% of MAGE-A3, 60% of MAGE-A4, 65% of MAGE-C2, and 20% of NY-ESO-1 at mRNA level. MAGE-A3 expression was associated with age, lymph node metastasis and tumor stage (all P<0.05), while MAGE-C2 expression was only associated with tumor stage (P<0.05). Furthermore, the MAGE-A3 expressing patients had a poorer overall survival (P<0.05). Multivariate analysis identified MAGE-A3 as an independent poor prognostic marker in ESCC. In vitro assay, ESCC cell lines treated with specific siRNAs to down-regulate MAGE-A3 and MAGE-C2 resulted in decreased colony-formation and migration ability (P<0.05). Epithelial marker E-cadherin was up-regulated in siRNA-MAGE-A3/C2 cells compared to controls, whereas mesenchymal markers Vimentin, N-cadherin and Slug were downregulated (all P<0.05), suggesting a role for MAGE-A3/C2 in ESCC metastasis through inducing epithelial-mesenchymal transition. The present study revealed that cancer-germline genes and their encoded proteins were frequently expressed in ESCC tumor samples and were related to poor prognosis. Thus, cancer-germline genes may serve as useful biomarkers and potential targets for ESCC patients.

Original languageEnglish (US)
Pages (from-to)793-803
Number of pages11
JournalHistology and histopathology
Volume32
Issue number8
DOIs
StatePublished - Aug 2017

Keywords

  • Biomarker
  • Cancer-germline genes
  • Epithelial-mesenchymal transition
  • Esophageal squamous cell carcinoma (ESCC)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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