Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I expression in nasopharyngeal carcinoma

被引:198
作者
Sengupta, Srikumar
den Boon, Johan A.
Chen, I-How
Newton, Michael A.
Dahl, David B.
Chen, Meng
Cheng, Yu-Juen
Westra, William H.
Chen, Chien-Jen
Hildesheim, Allan
Sugden, Bill
Ahlquist, Paul
机构
[1] Univ Wisconsin, Inst Mol Virol, Madison, WI 53706 USA
[2] Univ Wisconsin, Howard Hughes Med Inst, Madison, WI 53706 USA
[3] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA
[4] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA
[5] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA
[6] Texas A&M Univ, Dept Stat, College Stn, TX 77834 USA
[7] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA
[8] Johns Hopkins Med Inst, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA
[9] Natl Taiwan Univ, Taipei 10764, Taiwan
[10] MacKay Mem Hosp, Taipei 10764, Taiwan
关键词
D O I
10.1158/0008-5472.CAN-05-4399
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
To identify the molecular mechanisms by which EBV-associated epithelial cancers are maintained, we measured the expression of essentially all human genes and all latent EBV genes in a collection of 31 laser-captured, microdissected nasopharyngeal. carcinoma (NPC) tissue samples and 10 normal nasopharyngeal tissues. Global gene expression profiles clearly distinguished tumors from normal healthy epithelium. Expression levels of six viral genes (EBNA], EBNA2, EBNA3A, EBNA3B, LMP1, and LMP2A) were correlated among themselves and strongly inversely correlated with the expression of a large subset of host genes. Among the human genes whose inhibition was most strongly correlated with increased EBV gene expression were multiple MHC class I HLA genes involved in regulating immune response via antigen presentation. The association between EBV gene expression and inhibition of MHC class I HLA expression implies that antigen display is either directly inhibited by EBV, facilitating immune evasion by tumor cells, and/or that tumor cells with inhibited presentation are selected for their ability to sustain higher levels of EBV to take maximum advantage of EBV oncogene-mediated tumor-promoting actions. Our data clearly reflect such tumor promotion, showing that deregulation of key proteins involved in apoptosis (BCL2-related protein A1 and Fas apoptotic inhibitory molecule), cell cycle checkpoints (AKIP, SCYL1, and NIN), and metastasis (matrix metalloproteinase 1) is closely correlated with the levels of EBV gene expression in NPC.
引用
收藏
页码:7999 / 8006
页数:8
相关论文
共 70 条
[1]   Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUCH, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands [J].
Alos, L ;
Lujan, B ;
Castillo, M ;
Nadal, A ;
Carreras, M ;
Caballero, M ;
de Bolos, C ;
Cardesa, A .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2005, 29 (06) :806-813
[2]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[3]   MUC1 and nuclear β-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis [J].
Baldus, SE ;
Mönig, SP ;
Huxel, S ;
Landsberg, S ;
Hanisch, FG ;
Engelmann, K ;
Schneider, PM ;
Thiele, J ;
Hölscher, AH ;
Dienes, HP .
CLINICAL CANCER RESEARCH, 2004, 10 (08) :2790-2796
[4]   Expression of HER2 and C-KIT in nasopharyngeal carcinoma: Implications for a new therapeutic approach [J].
Bar-Sela, G ;
Kuten, A ;
Ben-Eliezer, S ;
Gov-Ari, E ;
Ben-Izhak, O .
MODERN PATHOLOGY, 2003, 16 (10) :1035-1040
[5]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[6]   Efficient downregulation of major histocompatibility complex class I molecules in human epithelial cells infected with cytomegalovirus [J].
Benz, C ;
Reusch, U ;
Muranyi, W ;
Brune, W ;
Atalay, R ;
Hengel, H .
JOURNAL OF GENERAL VIROLOGY, 2001, 82 :2061-2070
[7]   Human CD8+ T cell responses to EBV EBNA1:: HLA class I presentation of the (Gly-Ala)-containing protein requires exogenous processing [J].
Blake, N ;
Lee, S ;
Redchenko, I ;
Thomas, W ;
Steven, N ;
Leese, A ;
Steigerwald-Mullen, P ;
Kurilla, MG ;
Frappier, L ;
Rickinson, A .
IMMUNITY, 1997, 7 (06) :791-802
[8]   Construction, characterization, and complementation of a conditional-lethal DNA topoisomerase IIα mutant human cell line [J].
Carpenter, AJ ;
Porter, ACG .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (12) :5700-5711
[9]  
Chan JKC, 2005, PATHOLOGY GENETICS H, P85, DOI [10.1016/B978-0120884476/50006-4, DOI 10.1016/B978-0120884476/50006-4, 10.1016/B978-012088447-6/50006-4, DOI 10.1016/J.ORGGEOCHEM.2004.10.007]
[10]   HLA AND NASOPHARYNGEAL CARCINOMA IN CHINESE - A FURTHER STUDY [J].
CHAN, SH ;
DAY, NE ;
KUNARATNAM, N ;
CHIA, KB ;
SIMONS, MJ .
INTERNATIONAL JOURNAL OF CANCER, 1983, 32 (02) :171-176