TY - JOUR
T1 - Correlation between the high expression levels of cancer-germline genes with clinical characteristics in esophageal squamous cell carcinoma
AU - Chen, Xinfeng
AU - Wang, Liping
AU - Yue, Dongli
AU - Liu, Jinyan
AU - Huang, Lan
AU - Yang, Li
AU - Cao, Ling
AU - Qin, Guohui
AU - Li, Anqi
AU - Wang, Dan
AU - Wang, Meng
AU - Qi, Yu
AU - Zhang, Bin
AU - van der Bruggen, Pierre
AU - Zhang, Yi
N1 - Funding Information:
Acknowledgements. This work was supported by grants from the China-US (NFSC-NIH) Program for Biomedical Collaborative Research (Grant No.812111102), the National Natural Science Foundation of China (Grant No.81171986), Research Grant from the Ministry of Public Health (Grant No.20110110001), the Basic and Advanced Technology Research Foundation from Science and Technology Department of Henan Province (Grant No.122300410155), Creative Research Team of Higher Education of Henan Province and the Innovation Team of the First Affiliated Hospital of Zhengzhou University.
Publisher Copyright:
© 2017, Histology and Histopathology. All rights reserved.
PY - 2017/8
Y1 - 2017/8
N2 - 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.
AB - 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.
KW - Biomarker
KW - Cancer-germline genes
KW - Epithelial-mesenchymal transition
KW - Esophageal squamous cell carcinoma (ESCC)
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UR - http://www.scopus.com/inward/citedby.url?scp=85018878732&partnerID=8YFLogxK
U2 - 10.14670/HH-11-847
DO - 10.14670/HH-11-847
M3 - Article
C2 - 27868181
AN - SCOPUS:85018878732
SN - 0213-3911
VL - 32
SP - 793
EP - 803
JO - Histology and Histopathology
JF - Histology and Histopathology
IS - 8
ER -
