title: Correlation between the high expression levels of cancer-germline genes with clinical characteristics in esophageal squamous cell carcinoma.
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.
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Dongli
authors.initials: D
authors.lastname: Yue
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Cao
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Qin
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Anqi
authors.initials: A
authors.lastname: Li
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Cerebral Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Hematology/Oncology, School of Medicine, Northwestern University, Chicago, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Ludwig Institute for Cancer Research Brussels, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: van der Bruggen
authors.affiliation: Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.|School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.|Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, Henan, China. yizhang@zzu.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000235:genetics; D016896:Treatment Outcome; D014746:Vimentin / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C104948:CTAG1B protein, human; D015820:Cadherins; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; C405429:MAGEC2 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014746:Vimentin