Abstract
To identify the novel gene signatures and molecular markers of nasopharyngeal carcinoma (NPC) by integrated bioinformatics analysis of multiple gene expression profiling datasets. Seven published gene expression profiling studies and one of our unpublished works were reanalyzed to identify the common significantly dysregulated (CSD) genes in NPC. Overrepresentation analysis of cytogenetic bands, Gene Ontology (GO) categories, pathways were used to explore CSD genes functionally associated with carcinogenesis. The protein expressions of selected CSD genes were examined by immunohistochemistry on tissue microarrays, and the correlations of their expressions with clinical outcomes were evaluated. Using the criteria (genes reported deregulated in more than one study), a total of 962 genes were identified as the CSD genes in NPC. Four upregulated (BUB1B, CCND2, CENPF, and MAD2L1) and two downregulated (LTF and SLPI) genes were markedly reported in six studies. The enrichments of chromosome aberrations were 2q23, 2q31, 7p15, 12q15, 12q22, 18q11, and 18q12 in upregulated genes and 14q32 and 16q13 in downregulated genes. The activated GO categories and pathways related to proliferation, adhesion, invasion, and downregulated immune response had been functionally associated with NPC. SLPI significantly downregulated in nasopharyngeal adenocarcinoma. Furthermore, the high expression of BUB1B or CENPF was associated with poor overall survival of patients. It was first clearly identified the dysregulated expression of BUB1B and SLPI in NPC tissues. Further studies of the CSD genes as gene signatures and molecular markers of NPC might improve the understanding of the disease and identify new therapeutic targets.
Highlights
Nasopharyngeal carcinoma (NPC) is a malignant epithelial head and neck carcinoma that is highly prevalent in southern China and Southeast Asia [1]
Impact: Further studies of the common significantly dysregulated (CSD) genes as gene signatures and molecular markers of NPC might improve the understanding of the disease and identify new therapeutic targets
A total of 3,916 unique and mapped dysregulated genes were differentially expressed in the 8 independent gene expression profiling studies on NPC (Supplementary Fig. S1)
Summary
Nasopharyngeal carcinoma (NPC) is a malignant epithelial head and neck carcinoma that is highly prevalent in southern China and Southeast Asia [1]. Multiple molecular studies have reported that NPC is a highly. Authors' Affiliations: 1Cancer Research Institute, Disease genome Research Center, Central South University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; Key Laboratory of Carcinogenesis, Ministry of Health; 2Department of Medical Laboratory Science, Xiangya School of Medicine, Central South University, Changsha, Hunan; 3Medical Research Center, Peking University Third Hospital, Beijing; and 4The Center for Skull Base Surgery and Neurooncology, Hunan Province, China. Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). The mechanism of carcinogenesis and progression of NPC is not well understood. A clearer understanding of the molecular signature and underlying mechanisms would be beneficial in providing effective biomarkers for therapeutic planning and intervention
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