Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort.

Autor: Chin YM; Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia., Tan LP; Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia., Abdul Aziz N; Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia., Mushiroda T; Laboratory for Pharmacogenetics, RIKEN Center for Integrative Medical Sciences, Tsurumi-Ku, Yokohama, Kanagawa, Japan., Kubo M; Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Tsurumi-Ku, Yokohama, Kanagawa, Japan., Mohd Kornain NK; Department of Pathology, Faculty of Medicine, University Technology MARA (UiTM), Malaysia., Tan GW; Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia., Khoo AS; Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia., Krishnan G; Department of Otorhinolaryngology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia., Pua KC; Department of Otorhinolaryngology, Pulau Pinang General Hospital, Georgetown, Pulau Pinang, Malaysia., Yap YY; Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.; Department of Otorhinolaryngology, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia., Teo SH; Cancer Research Malaysia, Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia., Lim PV; Tung Shin Hospital, Jalan Pudu, Kuala Lumpur, Malaysia., Nakamura Y; Department of Medicine, University of Chicago, Chicago, IL., Lum CL; Department of Otorhinolaryngology, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia., Ng CC; Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2016 Oct 15; Vol. 139 (8), pp. 1731-9. Date of Electronic Publication: 2016 Jun 24.
DOI: 10.1002/ijc.30207
Abstrakt: Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway (pGWAS-GSEA  = 1.98 × 10(-2) ; pExpr-GSEA  = 1.27 × 10(-24) ; pBonf-Combined  = 4.15 × 10(-21) ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (pAmpliSeq-GSEA  = 6.56 × 10(-4) ). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort.
(© 2016 UICC.)
Databáze: MEDLINE
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