Deciphering the peptidome of urine from ovarian cancer patients and healthy controls

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• 作者：Christopher R Smith ; Ihor Batruch ; Josep Miquel Bau?a ; Hari Kosanam…
• 关键词：Biomarker ; Early diagnosis ; Mass spectrometry ; Ovarian cancer ; Urine peptidome
• 刊名：Clinical Proteomics
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：11
• 期：1
• 全文大小：313 KB
• 参考文献：1. Siegel, R, Naishadham, D, Jemal, A (2012) Cancer statistics, 2012. CA Cancer J Clin 62: pp. 10-29 CrossRef
  2. Bhoola, S, Hoskins, WJ (2006) Diagnosis and management of epithelial ovarian cancer. Obstet Gynecol 107: pp. 1399-1410 CrossRef
  3. Leung, F, Diamandis, EP, Kulasingam, V (2012) From bench to bedside: discovery of ovarian cancer biomarkers using high-throughput technologies in the past decade. Biomark Med 6: pp. 613-625 CrossRef
  4. Gelman, JS, Sironi, J, Castro, LM, Ferro, ES, Fricker, LD (2011) Peptidomic analysis of human cell lines. J Proteome Res 10: pp. 1583-1592 CrossRef
  5. Soloviev, M, Finch, P (2006) Peptidomics: bridging the gap between proteome and metabolome. Proteomics 6: pp. 744-747 CrossRef
  6. Liang, X, Huuskonen, J, Hajivandi, M, Manzanedo, R, Predki, P, Amshey, JR, Pope, RM (2009) Identification and quantification of proteins differentially secreted by a pair of normal and malignant breast-cancer cell lines. Proteomics 9: pp. 182-193 CrossRef
  7. Makridakis, M, Vlahou, A (2010) Secretome proteomics for discovery of cancer biomarkers. J Proteomics 73: pp. 2291-2305 CrossRef
  8. Koblinski, JE, Ahram, M, Sloane, BF (2000) Unraveling the role of proteases in cancer. Clin Chim Acta 291: pp. 113-135 CrossRef
  9. Villanueva, J, Shaffer, DR, Philip, J, Chaparro, CA, Erdjument-Bromage, H, Olshen, AB, Fleisher, M, Lilja, H, Brogi, E, Boyd, J, Sanchez-Carbayo, M, Holland, EC, Cordon-Cardo, C, Scher, HI, Tempst, P (2006) Differential exoprotease activities confer tumor-specific serum peptidome patterns. J Clin Invest 116: pp. 271-284 CrossRef
  10. Davis, MT, Auger, PL, Patterson, SD (2010) Cancer biomarker discovery via low molecular weight serum profiling–are we following circular paths?. Clin Chem 56: pp. 244-247 CrossRef
  11. Good, DM, Thongboonkerd, V, Novak, J, Bascands, JL, Schanstra, JP, Coon, JJ, Dominiczak, A, Mischak, H (2007) Body fluid proteomics for biomarker discovery: lessons from the past hold the key to success in the future. J Proteome Res 6: pp. 4549-4555 CrossRef
  12. Fredolini, C, Meani, F, Luchini, A, Zhou, W, Russo, P, Ross, M, Patanarut, A, Tamburro, D, Gambara, G, Ornstein, D, Odicino, F, Ragnoli, M, Ravaggi, A, Novelli, F, Collura, D, D’Urso, L, Muto, G, Belluco, C, Pecorelli, S, Liotta, L, Petricoin, EF (2010) Investigation of the ovarian and prostate cancer peptidome for candidate early detection markers using a novel nanoparticle biomarker capture technology. AAPS J 12: pp. 504-518 CrossRef
  13. Timms, JF, Cramer, R, Camuzeaux, S, Tiss, A, Smith, C, Burford, B, Nouretdinov, I, Devetyarov, D, Gentry-Maharaj, A, Ford, J, Luo, Z, Gammerman, A, Menon, U, Jacobs, I (2010) Peptides generated ex vivo from serum proteins by tumor-specific exopeptidases are not useful biomarkers in ovarian cancer. Clin Chem 56: pp. 262-271 CrossRef
  14. Petricoin, EF, Ardekani, AM, Hitt, BA, Levine, PJ, Fusaro, VA, Steinberg, SM, Mills, GB, Simone, C, Fishman, DA, Kohn, EC, Liotta, LA (2002) Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359: pp. 572-577 CrossRef
  15. Petricoin, EF, Ornstein, DK, Paweletz, CP, Ardekani, A, Hackett, PS, Hitt, BA, Velassco, A, Trucco, C, Wiegand, L, Wood, K, Simone, CB, Levine, PJ, Linehan, WM, Emmert-Buck, MR, Steinberg,
• 刊物主题：Cell Biology; Pathology; Biotechnology; Proteomics;
• 出版者：BioMed Central
• ISSN：1559-0275

文摘

Background Ovarian cancer (OvCa) is the most lethal gynecological malignancy. The emergence of high-throughput technologies, such as mass spectrometry, has allowed for a paradigm shift in the way we search for novel biomarkers. Urine-based peptidomic profiling is a novel approach that may result in the discovery of noninvasive biomarkers for diagnosing patients with OvCa. In this study, the peptidome of urine from 6 ovarian cancer patients and 6 healthy controls was deciphered. Results Urine samples underwent ultrafiltration and the filtrate was subjected to solid phase extraction, followed by fractionation using strong cation exchange chromatography. These fractions were analyzed using an Orbitrap mass spectrometer. Over 4600 unique endogenous urine peptides arising from 713 proteins were catalogued, representing the largest urine peptidome reported to date. Each specimen was processed in triplicate and reproducibility at the protein (69-76%) and peptide (58-63%) levels were noted. More importantly, over 3100 unique peptides were detected solely in OvCa specimens. One such promising biomarker was leucine-rich alpha-2-glycoprotein (LRG1), where multiple peptides were found in all urines from OvCa patients, but only one peptide was found in one healthy control urine sample. Conclusions Mining the urine peptidome may yield highly promising novel OvCa biomarkers.