title: Gene expression profile changes and possible molecular subtypes in differentiated-type nonkeratinizing nasopharyngeal carcinoma.
abstract: Nasopharyngeal carcinoma (NPC) is a human malignant tumor with a high incidence and a poor prognosis in Southern China and South-eastern Asia. In this study, we comprehensively analyzed the gene expression profiles in 24 samples of primary differentiated-type nonkeratining NPC (DNK-NPC) tissues, 24 samples of normal nasopharyngeal tissues and 4 DNK-NPC cell lines using cDNA microarray technology and bioinformatics methods. We found expression level of some genes was wildly alerted in the DNK-NPC samples. In addition, our hierarchical clustering analysis revealed 2 distinctive subtypes of gene expression patterns in DNK-NPC tissue samples. The discriminator genes were identified using a signal-to-noise (S(2)N) algorithm by permuting of the data set 10,000 times. To further characterize the clinical relevance of the tumor subtypes, we evaluated a surrogate marker, CCND2, differentially expressed between the 2 tumor subgroups by using immunohistochemistry in an independent set of 137 DNK-NPC samples. CCND2 was highly expressed in the subgroups with "aggressive" features and was associated with T classification (p = 0.006) and clinical stage (p = 0.013). Patients with high level of CCND2 expression had poorer overall survival than those with low level (p = 0.034). Our results suggest that DNK-NPC can be classified into 2 subtypes based on gene expression patterns, which can be used in determining prognosis and treatment of the tumor.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Zu-Guo
authors.initials: ZG
authors.lastname: Li
authors.forename: Juan
authors.initials: J
authors.lastname: Lu
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Fang
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Ding
authors.forename: Kai-Tai
authors.initials: KT
authors.lastname: Yao
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D009305:Nasopharynx / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C080336:CCND2 protein, human; D056742:Cyclin D2; D012333:RNA, Messenger