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 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.

MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma

“…Studies by Zeng et al (2007), using profiling and immunohistochemical stains, shows that the protein levels of these coregulated targets were significantly elevated in NPC tissues, whereas elevated expression of extracellular matrix proteins was shown by Sengupta et al (2008) using Q-PCR. The analysis is consistent with the observation that WNT signalling pathway is abnormally regulated in NPC (Shi et al, 2006;Zeng et al, 2007;Chou et al, 2008).…”

An Update on Epstein-Barr Virus and Nasopharyngeal Carcinogenesis

“…Other genes frequently inactivated by promoter methylation in NPC include TSCL1 at 11q23 and EDNRB at 13q22, E-cadherin, and death-associated protein kinase (DAPK) [34][35][36]. Gene expression profiling has shown dysregulation of the PI3K/Akt, WNT/b-catenin, TGF-b, and MAPK signaling pathways in NPC with upregulation of NF-jB2, survivin, Bcl-2 upregulation, nuclear accumulation of bcatenin, and dysregulation of integrins [37]. …”

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma

“…Although the radiotherapy can control early stage of NPC, tumor recurrence and distant metastasis are the key difficulties of NPC therapy 4, 5, 6, 7. At present, NPC tumorigenesis and progression are thought to be multistep processes involving multiple genetic and epigenetic changes 8, 9, 10, 11. Although molecular biology studies have improved general understanding of the tumorigenesis and progression of NPC, the appropriate biomarkers for metastasis mechanism have not yet been identified.…”