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

The Malaysian NPC Study Group

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 (p GWAS-GSEA = 1.98 × 10 −2 ; p Expr-GSEA = 1.27 × 10 −24 ; p Bonf-Combined = 4.15 × 10 −21 ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (p AmpliSeq-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.

Original languageEnglish
Pages (from-to)1731-1739
Number of pages9
JournalInternational Journal of Cancer
Volume139
Issue number8
DOIs
Publication statusPublished - 15-10-2016

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Axonemal Dyneins
Nasopharynx
Genome-Wide Association Study
Carcinoma
Mucociliary Clearance
Nasopharyngeal carcinoma
Gene Ontology
Cilia
Transcriptome
Respiratory Tract Infections
Genes
Single Nucleotide Polymorphism
Squamous Cell Carcinoma

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{38014e38c1de4e509907c16be975ee6a,
title = "Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort",
abstract = "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 (p GWAS-GSEA = 1.98 × 10 −2 ; p Expr-GSEA = 1.27 × 10 −24 ; p Bonf-Combined = 4.15 × 10 −21 ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (p AmpliSeq-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.",
author = "{The Malaysian NPC Study Group} and Chin, {Yoon Ming} and Tan, {Lu Ping} and {Abdul Aziz}, Norazlin and Taisei Mushiroda and Michiaki Kubo and {Mohd Kornain}, {Noor Kaslina} and Tan, {Geok Wee} and Khoo, {Alan Soo Beng} and Gopala Krishnan and Pua, {Kin Choo} and Yap, {Yoke Yeow} and Teo, {Soo Hwang} and Lim, {Paul Vey Hong} and Yusuke Nakamura and Lum, {Chee Lun} and Ng, {Ching Ching}",
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Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort. / The Malaysian NPC Study Group.

In: International Journal of Cancer, Vol. 139, No. 8, 15.10.2016, p. 1731-1739.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort

AU - The Malaysian NPC Study Group

AU - Chin, Yoon Ming

AU - Tan, Lu Ping

AU - Abdul Aziz, Norazlin

AU - Mushiroda, Taisei

AU - Kubo, Michiaki

AU - Mohd Kornain, Noor Kaslina

AU - Tan, Geok Wee

AU - Khoo, Alan Soo Beng

AU - Krishnan, Gopala

AU - Pua, Kin Choo

AU - Yap, Yoke Yeow

AU - Teo, Soo Hwang

AU - Lim, Paul Vey Hong

AU - Nakamura, Yusuke

AU - Lum, Chee Lun

AU - Ng, Ching Ching

PY - 2016/10/15

Y1 - 2016/10/15

N2 - 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 (p GWAS-GSEA = 1.98 × 10 −2 ; p Expr-GSEA = 1.27 × 10 −24 ; p Bonf-Combined = 4.15 × 10 −21 ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (p AmpliSeq-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.

AB - 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 (p GWAS-GSEA = 1.98 × 10 −2 ; p Expr-GSEA = 1.27 × 10 −24 ; p Bonf-Combined = 4.15 × 10 −21 ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (p AmpliSeq-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.

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