Spondin-2 (SPON2), a More Prostate-Cancer-Specific Diagnostic Biomarker

被引:54
作者
Qian, Xiaolong [1 ,2 ]
Li, Changling [3 ,4 ]
Pang, Bo [1 ]
Xue, Meng [1 ]
Wang, Jian [1 ]
Zhou, Jianguang [1 ]
机构
[1] Beijing Inst Biotechnol, Dept Med Mol Biol, Beijing, Peoples R China
[2] Tianjin Med Univ, Canc Hosp, State Key Lab Breast Canc Res, Dept Breast Pathol & Res, Tianjin, Peoples R China
[3] Peking Union Med Coll, Inst Canc, Beijing 100021, Peoples R China
[4] Chinese Acad Med Sci, Beijing 100730, Peoples R China
基金
中国国家自然科学基金;
关键词
MATRIX PROTEIN MINDIN; CELL-LINES; PROTEOMIC ANALYSIS; ANTIGEN; SERUM; DISCOVERY; LNCAP; MEN; IDENTIFICATION; MARKERS;
D O I
10.1371/journal.pone.0037225
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Prostate-specific antigen (PSA) screening, although common, has recently been called into question. To find prostate cancer (PCa) diagnostic biomarkers that can make up for the defects of PSA, we compared the secretomes of several benign and PCa cell lines, selected candidate molecules, and then confirmed their clinical value. Methodology/Principal Findings: We first identified extracellular proteins by two-dimensional gel electrophoresis (2-DE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification. We then validated the secreted proteins on a cellular level, and finally determined whether they could be used as PCa diagnostic biomarkers using prostate tissue and serum specimens of Chinese volunteers by immunohistostaining and sandwich ELISA. We obtained credible extracellular protein 2-DE graphs of prostate cell lines. The 5 spots that showed superior repeatability were selected for LC-MS/MS analysis, which identified seven candidate molecules. One of the candidate molecules, spondin-2 (SPON2), was only expressed in the conditioned media (CM) of androgen receptor (AR) positive PCa cell lines. Using tissue microarray by immunohistostaining, we found SPON2 to be over-expressed in PCa. SPON2 staining was more intense in Gleason score sum 7-8 and in PCa patients with metastasis. By receiver operator characteristic (ROC) curve analysis, we found that the serum SPON2 level was elevated in PCa patients, showing sensitivity and specificity suitable for diagnostic use. We also found that SPON2 could be used to identify PCa patients with serum PSA levels no higher than 10 ng/ml from healthy elderly men. Conclusion/Significance: SPON2 is a new serum and histological diagnostic biomarker for PCa. It can avoid some of the problems of PSA testing and was here found to offer relatively high sensitivity and specificity relative to PSA.
引用
收藏
页数:10
相关论文
共 26 条
[1]   Biology of prostate-specific antigen [J].
Balk, SP ;
Ko, YJ ;
Bubley, GJ .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (02) :383-391
[2]   The Secreted Protein Discovery Initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: A bioinformatics assessment [J].
Clark, HF ;
Gurney, AL ;
Abaya, E ;
Baker, K ;
Baldwin, D ;
Brush, J ;
Chen, J ;
Chow, B ;
Chui, C ;
Crowley, C ;
Currell, B ;
Deuel, B ;
Dowd, P ;
Eaton, D ;
Foster, J ;
Grimaldi, C ;
Gu, QM ;
Hass, PE ;
Heldens, S ;
Huang, A ;
Kim, HS ;
Klimowski, L ;
Jin, YS ;
Johnson, S ;
Lee, J ;
Lewis, L ;
Liao, DZ ;
Mark, M ;
Robbie, E ;
Sanchez, C ;
Schoenfeld, J ;
Seshagiri, S ;
Simmons, L ;
Singh, J ;
Smith, V ;
Stinson, J ;
Vagts, A ;
Vandlen, R ;
Watanabe, C ;
Wieand, D ;
Woods, K ;
Xie, MH ;
Yansura, D ;
Yi, S ;
Yu, GY ;
Yuan, J ;
Zhang, M ;
Zhang, ZM ;
Goddard, A ;
Wood, WI .
GENOME RESEARCH, 2003, 13 (10) :2265-2270
[3]   Total and free serum prostate specific antigen levels during the first month of acute prostatitis [J].
Gamé, X ;
Vincendeau, S ;
Palascak, R ;
Milcent, S ;
Fournier, R ;
Houlgatte, A .
EUROPEAN UROLOGY, 2003, 43 (06) :702-705
[4]  
Gansler T, 2010, CA-CANCER J CLIN, V60, P1, DOI [10.3322/caac.20073, 10.3322/caac.20049]
[5]   β-2-microglobulin is an androgen-regulated secreted protein elevated in serum of patients with advanced prostate cancer [J].
Gross, Mitchell ;
Top, Irina ;
Laux, Isett ;
Katz, Jonathan ;
Curran, John ;
Tindell, Charles ;
Agus, David .
CLINICAL CANCER RESEARCH, 2007, 13 (07) :1979-1986
[6]  
HAYWARD SW, 1995, IN VITRO CELL DEV-AN, V31, P14
[7]   The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens [J].
He, YW ;
Li, H ;
Zhang, J ;
Hsu, CL ;
Lin, E ;
Zhang, N ;
Guo, J ;
Forbush, KA ;
Bevan, MJ .
NATURE IMMUNOLOGY, 2004, 5 (01) :88-97
[8]   The extracellular matrix protein mindin serves as an integrin ligand and is critical for inflammatory cell recruitment [J].
Jia, W ;
Li, H ;
He, YW .
BLOOD, 2005, 106 (12) :3854-3859
[9]   R-spondin2 is a secreted activator of Wnt/β-catenin signaling and is required for Xenopus myogenesis [J].
Kazanskaya, O ;
Glinka, A ;
Barrantes, ID ;
Stannek, P ;
Niehrs, C ;
Wu, W .
DEVELOPMENTAL CELL, 2004, 7 (04) :525-534
[10]   R-Spondin family members regulate the Wnt pathway by a common mechanism [J].
Kim, Kyung-Ah ;
Wagle, Marie ;
Tran, Karolyn ;
Zhan, Xiaoming ;
Dixon, Melissa A. ;
Liu, Shouchun ;
Gros, Delphine ;
Korver, Wouter ;
Yonkovich, Shirlee ;
Tomasevic, Nenad ;
Binnerts, Minke ;
Abo, Arie .
MOLECULAR BIOLOGY OF THE CELL, 2008, 19 (06) :2588-2596