Grigoriadis Anita, Caballero Otavia L, Hoek Keith S, da Silva Leonard, Chen Yao-Tseng, Shin Sandra J, Jungbluth Achim A, Miller Lance D, Clouston David, Cebon Jonathan, Old Lloyd J, Lakhani Sunil R, Simpson Andrew J G, Neville A Munro
Ludwig Institute for Cancer Research, 605 Third Avenue, New York, NY 10158, USA.
Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13493-8. doi: 10.1073/pnas.0906840106. Epub 2009 Jul 27.
Cancer/testis (CT) genes are predominantly expressed in human germ line cells, but not somatic tissues, and frequently become activated in different cancer types. Several CT antigens have already proved to be useful biomarkers and are promising targets for therapeutic cancer vaccines. The aim of the present study was to investigate the expression of CT antigens in breast cancer. Using previously generated massively parallel signature sequencing (MPSS) data, together with 9 publicly available gene expression datasets, the expression pattern of CT antigens located on the X chromosome (CT-X) was interrogated. Whereas a minority of unselected breast cancers was found to contain CT-X transcripts, a significantly higher expression frequency was detected in estrogen and progesterone receptor (ER) negative breast cancer cell lines and primary breast carcinomas. A coordinated pattern of CT-X antigen expression was observed, with MAGEA and NY-ESO-1/CTAG1B being the most prevalent antigens. Immunohistochemical staining confirmed the correlation of CT-X antigen expression and ER negativity in breast tumors and demonstrated a trend for their coexpression with basal cell markers. Because of the limited therapeutic options for ER-negative breast cancers, vaccines based on CT-X antigens might prove to be useful.
癌/睾丸（CT）基因主要在人类生殖系细胞中表达，而不在体细胞组织中表达，并且在不同癌症类型中经常被激活。几种CT抗原已被证明是有用的生物标志物，并且是治疗性癌症疫苗的有前景的靶点。本研究的目的是调查CT抗原在乳腺癌中的表达。利用先前生成的大规模平行签名测序（MPSS）数据，以及9个公开可用的基因表达数据集，对位于X染色体上的CT抗原（CT-X）的表达模式进行了研究。虽然发现少数未经选择的乳腺癌含有CT-X转录本，但在雌激素和孕激素受体（ER）阴性的乳腺癌细胞系和原发性乳腺癌中检测到显著更高的表达频率。观察到CT-X抗原的协调表达模式，其中MAGEA和NY-ESO-1/CTAG1B是最普遍的抗原。免疫组织化学染色证实了CT-X抗原表达与乳腺肿瘤中ER阴性的相关性，并显示出它们与基底细胞标志物共表达的趋势。由于ER阴性乳腺癌的治疗选择有限，基于CT-X抗原的疫苗可能被证明是有用的。
