title: Panel of candidate biomarkers for renal cell carcinoma.
abstract: The timely diagnosis and therapeutic monitoring of human renal cell carcinoma (RCC) is limited by the lack of specific biomarkers. To identify candidate RCC biomarkers, we used 2-DE gel electrophoresis with mass spectrometry and 2-DE spot intensity-based ROC analysis to analyze 18 sets of paired normal and RCC tumor tissue including conventional, papillary, and chromophobe subtypes. Validation was performed with RCC patient plasma samples and confirmed by clustergram, shRNA, and immunohistochemistry assays. Cardinal candidates were evaluated by ELISA. The leading candidate biomarker that was upregulated in RCC samples according to the clustergram and validation analysis was nicotinamide N-methyltransferase (NNMT) (13/15, P < 0.0001). Other upregulated candidate biomarkers that were identified by this method include ferritin, hNSE, NM23, secretagogin, and L-plastin. The upregulation of NNMT in RCC was confirmed by immunoblotting and immunohistochemistry. Analysis of fractionated membrane-associated proteins identified CAP-G, mitofillin, tubulin alpha, RBBP7, and HSP27. Of these, RBBP7 and HSP27 were highly expressed in the chromophobe subtype of RCC (3/3) but were absent from conventional RCC (0/3). The triple combination of the NNMT, FTL, and hNSE biomarkers had the highest predictive capacity of 0.993, while NNMT was the single, most powerful candidate diagnostic biomarker for all types of RCC.
authors.affiliation: Research Division, DCD, Inc., Pohang Technopark, Pohang, Kyungbuk, 790-834, Korea.
authors.forename: Dong Su
authors.initials: DS
authors.lastname: Kim
authors.forename: Yoon Pyo
authors.initials: YP
authors.lastname: Choi
authors.forename: Suki
authors.initials: S
authors.lastname: Kang
authors.forename: Ming Qing
authors.initials: MQ
authors.lastname: Gao
authors.forename: Baekil
authors.initials: B
authors.lastname: Kim
authors.forename: Haeng Ran
authors.initials: HR
authors.lastname: Park
authors.forename: Young Deuk
authors.initials: YD
authors.lastname: Choi
authors.forename: Jong Baek
authors.initials: JB
authors.lastname: Lim
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Na
authors.forename: Hye Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: Young-Pyo
authors.initials: YP
authors.lastname: Nam
authors.forename: Mi Hyang
authors.initials: MH
authors.lastname: Moon
authors.forename: Hae Ree
authors.initials: HR
authors.lastname: Yun
authors.forename: Dong Hee
authors.initials: DH
authors.lastname: Lee
authors.forename: Won-Man
authors.initials: WM
authors.lastname: Park
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000378:metabolism*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D008875:Middle Aged; D050903:Nicotinamide N-Methyltransferase / Q000032:analysis / Q000378:metabolism*; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D012372:ROC Curve; D015203:Reproducibility of Results; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D020543:Proteome; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase