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

详细信息    查看全文

• 作者：Yoon-Ming Chin ; Lu Ping Tan ; Norazlin Abdul Aziz ; Taisei Mushiroda ; Michiaki Kubo ; Noor Kaslina Mohd Kornain ; Geok Wee Tan ; Alan Soo-Beng Khoo ; Gopala Krishnan ; Kin-Choo Pua ; Yoke-Yeow Yap ; Soo-Hwang Teo ; Paul Vey-Hong Lim ; Yusuke Nakamura ; Chee Lun Lum ; The Malaysian NPC Study Group and Ching-Ching Ng
• 刊名：International Journal of Cancer
• 出版年：2016
• 出版时间：15 October 2016
• 年：2016
• 卷：139
• 期：8
• 页码：1731-1739
• 全文大小：302K
• ISSN：1097-0215

文摘

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.