Cancer-testis gene expression profiling in esophageal squamous cell carcinoma Identification of specific tumor marker and potential targets for immunotherapy

被引:43
作者
Forghanifard, Mohammad Mahdi [1 ,2 ]
Gholamin, Mehran [1 ]
Farshchian, Moein [1 ]
Moaven, Omeed [1 ,3 ]
Memar, Bahram [4 ]
Forghani, Mohammad Naser [5 ]
Dadkhah, Ezzat [1 ]
Naseh, Hossein [4 ]
Moghbeli, Meysam [1 ]
Raeisossadati, Reza [1 ]
Abbaszadegan, Mohammad Reza [1 ]
机构
[1] Mashhad Univ Med Sci, Div Human Genet, Immunol Res Ctr, Avicenna Res Inst, Mashhad, Iran
[2] Islamic Azad Univ, Dept Biol, Sci & Res Branch, Tehran, Iran
[3] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA
[4] MUMS, Omid Hosp, Dept Pathol, Mashhad, Iran
[5] MUMS, Omid Hosp, Dept Surg, Mashhad, Iran
关键词
esophageal squamous cell carcinoma; cancer testis antigens; real-time PCR; tumor marker; cancer vaccine; PROTEIN-PROTEIN INTERACTION; MAGE GENES; CANCER/TESTIS ANTIGENS; IMMUNOHISTOCHEMICAL EXPRESSION; HETEROGENEOUS EXPRESSION; NY-ESO-1; EXPRESSION; GROWTH-FACTOR; STEM-CELLS; MAGE-A3/4; GANKYRIN;
D O I
10.4161/cbt.12.3.15949
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cancer-testis antigens (CTAs) are often specifically expressed in cancer cells and under normal conditions are only considered to be expressed in the germ line cells and the placenta. CTAs are potential targets for cancer immunotherapy and therefore necessitates their expression profiling. The expression profile of LAGE1, MAGE-A4 and NY-ESO1, their possible correlations and interaction, and the clinicopathological associations of each marker were studied. RNA was extracted from fresh esophagectomy tissues of 41 esophageal squamous cell carcinoma (ESCC) patients prior to any other therapeutic intervention. The relative mRNA expression of LAGE1, MAGE-A4 and NY-ESO1 was assessed with the real-time reverse transcription-polymerase chain reaction (RT-PCR) 5' nuclease assay. The overexpression of LAGE1, MAGE-A4 and NY-ESO1 was found in 39, 90.2 and 41.4% of ESCC samples respectively. Of the patients, 97.5% showed an overexpression of at least one CTA. The relative expression of MAGE-A4 was directly associated with lymph node metastasis and the stage of the tumor (p < 0.05). A significant direct correlation was also detected between the MAGE-A4/LAGE1 and MAGE-A4/NY-ESO1 levels of gene expression. MAGE-A4 is identified as a specific biomarker of ESCC with a possible oncogenic role contributing to tumor progression. Interactions between MAGE-A4, LAGE1 and NY-ESO1 and their significant clinical consequences introduce these CTAs as appropriate targets for a polyvalent cancer vaccine.
引用
收藏
页码:191 / 197
页数:7
相关论文
共 54 条
[41]  
Putz E, 1999, CANCER RES, V59, P241
[42]  
Quillien V, 1997, ANTICANCER RES, V17, P387
[43]   A cleaved form of MAGE-A4 binds to Miz-1 and induces apoptosis in human cells [J].
Sakurai, T ;
Itoh, K ;
Higashitsuji, H ;
Nagao, T ;
Nonoguchi, K ;
Chiba, T ;
Fujita, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (15) :15505-15514
[44]   Expression of cancer/testis tumor associated antigens in cervical squamous cell carcinoma [J].
Sarcevic, B ;
Spagnoli, GC ;
Terracciano, L ;
Schultz-Thater, E ;
Heberer, M ;
Gamulin, M ;
Krajina, Z ;
Oresic, T ;
Separovic, R ;
Juretic, A .
ONCOLOGY, 2003, 64 (04) :443-449
[45]  
TAGHAVI N, BMC CANC, V10, P138
[46]   Functional domains of necdin for protein-protein interaction, nuclear matrix targeting, and cell growth suppression [J].
Taniura, H ;
Kobayashi, M ;
Yoshikawa, K .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2005, 94 (04) :804-815
[47]   EXPRESSION OF MAGE-1 GENE BY ESOPHAGEAL CARCINOMAS [J].
TOH, Y ;
YAMANA, H ;
SHICHIJO, S ;
FUJITA, H ;
TOU, U ;
SAKAGUCHI, M ;
KAKEGAWA, T ;
ITOH, K .
JAPANESE JOURNAL OF CANCER RESEARCH, 1995, 86 (08) :714-717
[48]  
VERGATI M, 2010, J BIOMED BI IN PRESS
[49]  
Xiao J, 2004, WORLD J GASTROENTERO, V10, P1849
[50]  
Yamanaka K, 1998, INT J MOL MED, V2, P57