Premium
Multiple dysregulated pathways in nasopharyngeal carcinoma revealed by gene expression profiling
Author(s) -
Shi Wei,
Bastianutto Carlo,
Li Anna,
PerezOrdonez Bayardo,
Ng Raymond,
Chow KanYan,
Zhang Wendy,
Jurisica Igor,
Lo KwokWai,
Bayley Andrew,
Kim John,
O'Sullivan Brian,
Siu Lillian,
Chen Eric,
Liu FeiFei
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22107
Subject(s) - nasopharyngeal carcinoma , survivin , wnt signaling pathway , gene expression profiling , cancer research , biology , microarray , dna microarray , pathology , downregulation and upregulation , gene expression , signal transduction , medicine , radiation therapy , gene , cancer , biochemistry
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 NFκB2 and survivin play central roles in increasing resistance to apoptosis, and changes in integrin and WNT/β‐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. © 2006 Wiley‐Liss, Inc.