title: Multiple dysregulated pathways in nasopharyngeal carcinoma revealed by gene expression profiling.
abstract: Gene expression profiling was conducted using primary human nasopharyngeal carcinoma (NPC) biopsy samples to improve the understanding of the molecular pathways defining NPC and to identify novel potential therapeutic targets. RNA samples were extracted from 36 patients suspected to have NPC and hybridized onto the Affymetrix U133A chip. NPC was diagnosed in 19 patients, 11 had lymphoid hyperplasia (LH), and 6 were "normal" biopsies. Clinical stages for these NPC patients ranged from I-IV, including one M1. All NPC patients (except the M1) were treated with curative intent, which included radiotherapy alone (4 patients), or combined with chemotherapy (14 patients). Unsupervised clustering demonstrated a distinct NPC expression pattern, compared to normal biopsies. Subsequent Significance Analysis of Microarrays (SAM) derived from 14 NPC and 6 normal samples discovered 1,089 differentially regulated genes. Pathway analyses revealed novel insights into the mechanisms leading to NPC, whereby upregulation of NFkappaB2 and survivin play central roles in increasing resistance to apoptosis, and changes in integrin and WNT/beta-catenin signaling leading to uncontrolled proliferation. The role of survivin in resisting apoptosis in NPC was confirmed by RNA interference. Our data provide novel insights into the development and progression of NPC, and suggest survivin as a novel therapeutic target for NPC.
authors.affiliation: Division of Applied Molecular Oncology, Ontario Cancer Institute, Toronto, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Carlo
authors.initials: C
authors.lastname: Bastianutto
authors.forename: Anna
authors.initials: A
authors.lastname: Li
authors.forename: Bayardo
authors.initials: B
authors.lastname: Perez-Ordonez
authors.forename: Raymond
authors.initials: R
authors.lastname: Ng
authors.forename: Kan-Yan
authors.initials: KY
authors.lastname: Chow
authors.forename: Wendy
authors.initials: W
authors.lastname: Zhang
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.forename: Kwok-Wai
authors.initials: KW
authors.lastname: Lo
authors.forename: Andrew
authors.initials: A
authors.lastname: Bayley
authors.forename: John
authors.initials: J
authors.lastname: Kim
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: Lillian
authors.initials: L
authors.lastname: Siu
authors.forename: Eric
authors.initials: E
authors.lastname: Chen
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D016023:Integrins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit / Q000235:genetics / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000077022:Survivin; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D016023:Integrins; D008869:Microtubule-Associated Proteins; D052003:NF-kappa B p52 Subunit; C498206:NFKB2 protein, human; D009363:Neoplasm Proteins; D000077022:Survivin; D051153:Wnt Proteins; D051176:beta Catenin