title: Identification of candidate nasopharyngeal carcinoma serum biomarkers by cancer cell secretome and tissue transcriptome analysis: potential usage of cystatin A for predicting nodal stage and poor prognosis.
abstract: Nasopharyngeal carcinoma (NPC) is usually diagnosed at advanced clinical stages, resulting in poor outcomes. To discover serum biomarkers for improved NPC diagnosis and/or management, we simultaneously analyzed the NPC cell secretome and tissue transcriptome to identify candidate genes/proteins that are highly upregulated in NPC tissues and also secreted/released from NPC cells. Among the 30 candidates identified, 11 proteins were chosen for further validation using the serum samples from NPC patients and healthy controls, including cystatin A, cathepsin B, manganese superoxide dismutase and matrix metalloproteinase 2. The results showed that serum levels of all the four proteins were indeed higher in NPC patients versus healthy controls and that the use of a three-marker panel (cystatin A, manganese superoxide dismutase and matrix metalloproteinase 2) can contribute to a better NPC detection than each marker alone. In addition, a higher pretreated serum level of cystatin A was found to be associated with a higher nodal stage and poorer prognosis of NPC patients and cystatin A could modulate the migration and invasion of NPC cells in vitro. Altogether, our results indicate that analysis of both the cancer cell secretome and tissue transcriptome is a feasible strategy for efficient identification of novel NPC serum marker panel.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.
authors.forename: Kai-Ping
authors.initials: KP
authors.lastname: Chang
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Wu
authors.forename: Hua-Chien
authors.initials: HC
authors.lastname: Chen
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Peng
authors.forename: Ngan-Ming
authors.initials: NM
authors.lastname: Tsang
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Lee
authors.forename: Shiau-Chin
authors.initials: SC
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.forename: Yun-Shien
authors.initials: YS
authors.lastname: Lee
authors.forename: Sheng-Po
authors.initials: SP
authors.lastname: Hao
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002853:Chromatography, Liquid; D055312:Cystatin A / Q000097:blood*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D015203:Reproducibility of Results; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D055312:Cystatin A; D009363:Neoplasm Proteins