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

被引:14
作者
Chen, Xinfeng [1 ,2 ]
Wang, Liping [1 ,2 ]
Yue, Dongli [1 ,2 ]
Liu, Jinyan [1 ,3 ]
Huang, Lan [1 ]
Yang, Li [1 ]
Cao, Ling [1 ,2 ]
Qin, Guohui [1 ,2 ]
Li, Anqi [1 ,2 ]
Wang, Dan [1 ]
Wang, Meng [1 ,4 ]
Qi, Yu [5 ]
Zhang, Bin [6 ]
van der Bruggen, Pierre [7 ]
Zhang, Yi [1 ,2 ,3 ,8 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Biotherapy Ctr, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Oncol, Zhengzhou, Henan, Peoples R China
[3] Zhengzhou Univ, Sch Life Sci, Zhengzhou, Henan, Peoples R China
[4] Zhengzhou Univ, Affiliated Hosp 1, Dept Gastroenterol, Zhengzhou, Henan, Peoples R China
[5] Zhengzhou Univ, Affiliated Hosp 1, Dept Cerebral Surg, Zhengzhou, Henan, Peoples R China
[6] Northwestern Univ, Sch Med, Dept Hematol Oncol, Chicago, IL USA
[7] Catholic Univ Louvain, de Duve Inst, Ludwig Inst Canc Res Brussels, Brussels, Belgium
[8] Engn Key Lab Cell Therapy Henan Prov, Zhengzhou, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
Esophageal squamous cell carcinoma (ESCC); Cancer-germline genes; Biomarker; Epithelial-mesenchymal transition; CYTOLYTIC T-LYMPHOCYTES; TESTIS ANTIGEN; TUMOR-ANTIGEN; MAGE-A; HEPATOCELLULAR-CARCINOMA; HETEROGENEOUS EXPRESSION; CANCER/TESTIS ANTIGENS; PROGNOSTIC RELEVANCE; LUNG-CANCER; MELANOMA;
D O I
10.14670/HH-11-847
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 down regulation 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.
引用
收藏
页码:793 / 803
页数:11
相关论文
共 62 条
[1]   Heterogeneous expression of GAGE, NY-ESO-1, MAGE-A and SSX proteins in esophageal cancer: Implications for immunotherapy [J].
Akcakanat, A ;
Kanda, T ;
Tanabe, T ;
Komukai, S ;
Yajima, K ;
Nakagawa, S ;
Ohashi, M ;
Hatakeyama, K .
INTERNATIONAL JOURNAL OF CANCER, 2006, 118 (01) :123-128
[2]   Regulation of cancer germline antigen gene expression: implications for cancer immunotherapy [J].
Akers, Stacey N. ;
Odunsi, Kunle ;
Karpf, Adam R. .
FUTURE ONCOLOGY, 2010, 6 (05) :717-732
[3]   CD4+ T Effectors Specific for the Tumor Antigen NY-ESO-1 Are Highly Enriched at Ovarian Cancer Sites and Coexist with, but Are Distinct from, Tumor-Associated Treg [J].
Ayyoub, Maha ;
Pignon, Pascale ;
Classe, Jean-Marc ;
Odunsi, Kunle ;
Valmori, Danila .
CANCER IMMUNOLOGY RESEARCH, 2013, 1 (05) :303-308
[4]   Peptide Splicing in the Proteasome Creates a Novel Type of Antigen with an Isopeptide Linkage [J].
Berkers, Celia R. ;
de Jong, Annemieke ;
Schuurman, Karianne G. ;
Linnemann, Carsten ;
Geenevasen, Jan A. J. ;
Schumacher, Ton N. M. ;
Rodenko, Boris ;
Ovaa, Huib .
JOURNAL OF IMMUNOLOGY, 2015, 195 (09) :4075-4084
[5]   Expression of MAGE-A1-A12 subgroups in the invasive tumor front and tumor center in oral squamous cell carcinoma [J].
Brisam, M. ;
Rauthe, S. ;
Hartmann, S. ;
Linz, C. ;
Brands, R. C. ;
Kuebler, A. C. ;
Rosenwald, A. ;
Mueller-Richter, U. D. .
ONCOLOGY REPORTS, 2016, 35 (04) :1979-1986
[6]   MAGE-A 3/4 and NY-ESO-1 antigens expression in metastatic esophageal squamous cell carcinoma [J].
Bujas, T. ;
Marusic, Z. ;
Balja, M. Peric ;
Mijic, A. ;
Kruslin, B. ;
Tomas, D. .
EUROPEAN JOURNAL OF HISTOCHEMISTRY, 2011, 55 (01) :39-43
[7]   Effects of CT-Xp Gene Knock down in Melanoma Cell Lines [J].
Caballero, Otavia L. ;
Cohen, Tzeela ;
Gurung, Sita ;
Chua, Ramon ;
Lee, Peishan ;
Chen, Yao-Tseng ;
Jat, Parmjit ;
Simpson, Andrew J. G. .
ONCOTARGET, 2013, 4 (04) :531-541
[8]   Cancer/testis (CT) antigens: Potential targets for immunotherapy [J].
Caballero, Otavia L. ;
Chen, Yao-Tseng .
CANCER SCIENCE, 2009, 100 (11) :2014-2021
[9]   Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library [J].
Chen, YT ;
Güre, AO ;
Tsang, S ;
Stockert, E ;
Jäger, E ;
Knuth, A ;
Old, LJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (12) :6919-6923
[10]   Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy [J].
Coulie, Pierre G. ;
Van den Eynde, Benoit J. ;
van der Bruggen, Pierre ;
Boon, Thierry .
NATURE REVIEWS CANCER, 2014, 14 (02) :135-146