Correlation between the high expression levels of cancer-germline genes with clinical characteristics in esophageal squamous cell carcinoma
Xinfeng Chen1,2, Liping Wang1,2, Dongli Yue1,2, Jinyan Liu1,3, Lan Huang1, Li Yang1, Ling Cao1,2, Guohui Qin1,2, Anqi Li1,2, Dan Wang1, Meng Wang1,4, Yu Qi5, Bin Zhang6, Pierre van der Bruggen7 and Yi Zhang1,2,3,8
1Biotherapy Center, 2Department of Oncology, the First Affiliated Hospital of Zhengzhou University, 3School of Life Sciences, Zhengzhou University, Zhengzhou 4Department of Gastroenterology, 5Department of Cerebral Surgery, the First Affiliated Hospital of Zhengzhou University, Henan, China, 6Department of Hematology/Oncology, School of Medicine, Northwestern University, Chicago, USA, 7Ludwig Institute for Cancer Research Brussels, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium and 8Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, Henan, China
Offprint requests to: Dr. Yi Zhang, Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. e-mail: yizhang@zzu.edu.cn
Summary. 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. Histol Histopathol 32, 793-803 (2017)
Key words: Esophageal squamous cell carcinoma (ESCC), Cancer-germline genes, Biomarker, Epithelial-mesenchymal transition
DOI: 10.14670/HH-11-847