**6. Conclusion**

The molecular characterization, dissection and appreciation of carcinogenesis is, undoubtedly, much more complex than we ever envisaged. The disease of cancer *per se*  remains complicated, unpredictable and multifaceted – either by the impact and influence of genes, the environment, behaviour, proteins or all combined (epigenetics). In this chapter we have discussed the solid tumour of prostate cancer, a disease which falls in to two classes – indolent or aggressive. Pathologically, via immunohistology the disease 'looks' very different but at early and intermediate stages, clinically, we find it difficult to differentiate benign from malignant. We struggle to decide which glands can be left and monitored versus which that need resection and immediate therapy. The influence of 'omics and especially proteomics now has the power to categorize prostate cancer – not just the disease itself but possibly those men who may be prone to developing prostate cancer, especially the aggressive form and identify those men who need immediate intervention (Larkin et al., 2011). The next decade will see huge strides in stratifying 'normo' physiology and disease and we have presented a wealth of information here which helps to explain how the stateof-the-art methodologies and excellent clinical and patient stratification we currently have will enable this.

#### **7. References**

352 Biomarker

Fig. 8. Schematic nESI designs that allow its operation at the low nL/mL flow regime. Geometries, dimensions, along with their material compositions all play a pivotal role in the

The molecular characterization, dissection and appreciation of carcinogenesis is, undoubtedly, much more complex than we ever envisaged. The disease of cancer *per se*  remains complicated, unpredictable and multifaceted – either by the impact and influence of genes, the environment, behaviour, proteins or all combined (epigenetics). In this chapter we have discussed the solid tumour of prostate cancer, a disease which falls in to two classes – indolent or aggressive. Pathologically, via immunohistology the disease 'looks' very different but at early and intermediate stages, clinically, we find it difficult to differentiate benign from malignant. We struggle to decide which glands can be left and monitored versus which that need resection and immediate therapy. The influence of 'omics and especially proteomics now has the power to categorize prostate cancer – not just the disease itself but possibly those men who may be prone to developing prostate cancer, especially the aggressive form and identify those men who need immediate intervention (Larkin et al., 2011). The next decade will see huge strides in stratifying 'normo' physiology and disease and we have presented a wealth of information here which helps to explain how the stateof-the-art methodologies and excellent clinical and patient stratification we currently have

optimal nESI process (Lion et al., 2003).

**6. Conclusion** 

will enable this.


The Discovery of Cancer Tissue Specific Proteins in Serum: Case Studies on Prostate Cancer 355

Fournier, M. L., Gilmore, J. M., Martin-Brown, S. A., & Washburn, M. P. (2007).

Garbis, S., Lubec, G., & Fountoulakis, M. (2005). Limitations of current proteomics

Garbis, S. D., Melse-Boonstra, A., West, C. E., & van Breemen, R. B. (2001). Determination of

Garbis, S. D., Roumeliotis, T. I., Tyritzis, S. I., Zorpas, K. M., Pavlakis, K., & Constantinides,

Garbis, S. D., Tyritzis, S. I., Roumeliotis, T., Zerefos, P., Giannopoulou, E. G., Vlahou, A., et

Garcia-Ramirez, M., Canals, F., Hernandez, C., Colome, N., Ferrer, C., Carrasco, E., et al.

Gerber, S. A., Rush, J., Stemman, O., Kirschner, M. W., & Gygi, S. P. (2003). Absolute

Glen, A., Gan, C. S., Hamdy, F. C., Eaton, C. L., Cross, S. S., Catto, J. W. F., et al. (2008).

Lack of Protection Against Oxidative Damage. *Prostate, 71*(8), 824-834. Gottschlich, N., Culbertson, C. T., McKnight, T. E., Jacobson, S. C., & Ramsey, J. M. (2000).

of proteins and peptides. *J Chromatogr B Biomed Sci Appl, 745*(1), 243-249. Granger, J., Siddiqui, J., Copeland, S., & Remick, D. (2005). Albumin depletion of human

Grisendi, S., Mecucci, C., Falini, B., & Pandolfi, P. P. (2006). Nucleophosmin and cancer.

Gundry, R. L., White, M. Y., Nogee, J., Tchernyshyov, I., & Van Eyk, J. E. (2009). Assessment

technologies. *Journal of Chromatography A, 1077*(1), 1-18.

mass spectrometry. *Analytical Chemistry, 73*(22), 5358-5364.

Benign Prostate Hyperplasia. *Analytical Chemistry, 83*(3), 708-718.

spectrometry. *Journal of Proteome Research, 7*(8), 3146-3158.

*Proc Natl Acad Sci U S A, 100*(12), 6940-6945.

*5*(18), 4713-4718.

*Nature Reviews Cancer, 6*(7), 493-505.

*Proteomics, 9*(7), 2021-2028.

3654-3686.

Multidimensional separations-based shotgun proteomics. *Chemical Reviews, 107*(8),

folates in human plasma using hydrophilic interaction chromatography-tandem

C. A. (2011). A Novel Multidimensional Protein Identification Technology Approach Combining, Protein Size Exclusion Prefractionation, Peptide Zwitterion-Ion Hydrophilic Interaction Chromatography, and Nano-Ultraperformance RP Chromatography/nESI-MS(2) for the in-Depth Analysis of the Serum Proteome and Phosphoproteome: Application to Clinical Sera Derived from Humans with

al. (2008). Search for potential markers for prostate cancer diagnosis, prognosis and treatment in clinical tissue specimens using amine-specific isobaric tagging (iTRAQ) with two-dimensional liquid chromatography and tandem mass

(2007). Proteomic analysis of human vitreous fluid by fluorescence-based difference gel electrophoresis (DIGE): a new strategy for identifying potential candidates in the pathogenesis of proliferative diabetic retinopathy. *Diabetologia, 50*(6), 1294-1303.

quantification of proteins and phosphoproteins from cell lysates by tandem MS.

iTRAQ - Facilitated proteomic analysis of human prostate cancer cells identifies proteins associated with progression. *Journal of Proteome Research, 7*(3), 897-907. Goldstraw, M. A., Fitzpatrick, J. M., & Kirby, R. S. (2007). What is the role of inflammation in the pathogenesis of prostate cancer? *Bju International, 99*(5), 966-968. Gonzalez-Moreno, O., Boque, N., Redrado, M., Milagro, F., Campion, J., Endermann, T., et

al. (2011). Selenoprotein-P is Down-Regulated in Prostate Cancer, Which Results in

Integrated microchip-device for the digestion, separation and postcolumn labeling

plasma also removes low abundance proteins including the cytokines. *Proteomics,* 

of albumin removal from an immunoaffinity spin column: critical implications for proteomic examination of the albuminome and albumin-depleted samples.


Culbertson, C. T., Jacobson, S. C., & Michael Ramsey, J. (2002). Diffusion coefficient

Culbertson, C. T., Ramsey, R. S., & Ramsey, J. M. (2000). Electroosmotically induced

Culbertson, C. T., Tugnawat, Y., Meyer, A. R., Roman, G. T., Ramsey, J. M., & Gonda, S. R.

Dabbous, M. K., Jefferson, M. M., Haney, L., & Thomas, E. L. (2011). Biomarkers of

Das, S. K., Eder, S., Schauer, S., Diwoky, C., Temmel, H., Guertl, B., et al. (2011). Adipose

De Leon, J. T., Iwai, A., Feau, C., Garcia, Y., Balsiger, H. A., Storer, C. L., et al. (2011).

De Marzo, A. M., DeWeese, T. L., Platz, E. A., Meeker, A. K., Nakayama, M., Epstein, J. I., et

De Nunzio, C., Freedland, S. J., Miano, R., Trucchi, A., Cantiani, A., Carluccini, A., et al.

DeSouza, L., Diehl, G., Rodrigues, M. J., Guo, J. Z., Romaschin, A. D., Colgan, T. J., et al.

Diamandis, E. P. (2004). Mass Spectrometry as a diagnostic and a cancer biomarker

Dong, Y., Zhang, H. T., Hawthorn, L., Ganther, H. E., & Ip, C. (2003). Delineation of the

Everley, P. A., Krijgsveld, J., Zetter, B. R., & Gygi, S. P. (2004). Quantitative cancer

by oligonucleotide array. *Cancer Research, 63*(1), 52-59.

Prostate Cancer Is Diagnosed on Biopsy. *Prostate, 71*(14), 1492-1498. DeMarzo, A. M., Nelson, W. G., Isaacs, W. B., & Epstein, J. I. (2003). Pathological and

tandem mass spectrometry. *Journal of Proteome Research, 4*(2), 377-386. Di Cristofano, C., Leopizzi, M., Miraglia, A., Sardella, B., Moretti, V., Ferrara, A., et al.

molecular aspects of prostate cancer. *Lancet, 361*(9361), 955-964.

*of Sciences of the United States of America, 108*(29), 11878-11883.

hydraulic pumping on microchips: differential ion transport. *Analytical Chemistry,* 

(2005). Microchip separations in reduced-gravity and hypergravity environments.

metastatic potential in cultured adenocarcinoma clones. *Clinical & Experimental* 

Triglyceride Lipase Contributes to Cancer-Associated Cachexia. *Science, 333*(6039),

Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells. *Proceedings of the National Academy* 

al. (2004). Pathological and molecular mechanisms of prostate carcinogenesis: Implications for diagnosis, detection, prevention, and treatment. *Journal of Cellular* 

(2011). Metabolic Syndrome Is Associated With High Grade Gleason Score When

(2005). Search for cancer markers from endometrial tissues using differentially labeled tags iTRAQ and clCAT with multidimensional liquid chromatography and

(2010). Phosphorylated ezrin is located in the nucleus of the osteosarcoma cell.

discovery tool - Opportunities and potential limitations. *Molecular & Cellular* 

molecular basis for selenium-induced growth arrest in human prostate cancer cells

proteomics: Stable isotope labeling with amino acids in cell culture (SILAC) as a tool for prostate cancer research. *Molecular & Cellular Proteomics, 3*(7), 729-735. Farrah, T., Deutsch, E. W., Omenn, G. S., Campbell, D. S., Sun, Z., Bletz, J. A., et al. (2011). A

high-confidence human plasma proteome reference set with estimated concentrations in PeptideAtlas. *Molecular & Cellular Proteomics, 10*(9), M110 006353.

measurements in microfluidic devices. *Talanta, 56*(2), 365-373.

*72*(10), 2285-2291.

233-238.

*Metastasis, 28*(2), 101-111.

*Biochemistry, 91*(3), 459-477.

*Modern Pathology, 23*(7), 1012-1020.

*Proteomics, 3*(4), 367-378.

*Analytical Chemistry, 77*(24), 7933-7940.


The Discovery of Cancer Tissue Specific Proteins in Serum: Case Studies on Prostate Cancer 357

Kocher, T., & Superti-Furga, G. (2007). Mass spectrometry-based functional proteomics: from molecular machines to protein networks. *Nature Methods, 4*(10), 807-815. Koster, S., & Verpoorte, E. (2007). A decade of microfluidic analysis coupled with electrospray mass spectrometry: An overview. *Lab on a Chip, 7*(11), 1394-1412. Krust, B., El Khoury, D., Nondier, I., Soundaramourty, C., & Hovanessian, A. G. (2011).

Kuemmerle, N. B., Rysman, E., Lombardo, P. S., Flanagan, A. J., Lipe, B. C., Wells, W. A., et

Kuzyk, M. A., Smith, D., Yang, J., Cross, T. J., Jackson, A. M., Hardie, D. B., et al. (2009).

proteins in human plasma. *Molecular & Cellular Proteomics, 8*(8), 1860-1877. Larkin, S. E., Holmes, S., Cree, I. A., Walker, T., Basketter, V., Bickers, B., et al. (2011).

Lin, B. Y., White, J. T., Lu, W., Xie, T., Utleg, A. G., Yan, X. W., et al. (2005). Evidence for the

Lion, N., Rohner, T. C., Dayon, L., Arnaud, I. L., Damoc, E., Youhnovski, N., et al. (2003). Microfluidic systems in proteomics. *Electrophoresis, 24*(21), 3533-3562. Liu, T., Belov, M. E., Jaitly, N., Qian, W. J., & Smith, R. D. (2007). Accurate mass

Lubec, G., & Afjehi-Sadat, L. (2007). Limitations and pitfalls in protein identification by mass

Mann, M., & Kelleher, N. L. (2008). Precision proteomics: The case for high resolution and

Martin, D. B., Gifford, D. R., Wright, M. E., Keller, A., Yi, E., Goodlett, D. R., et al. (2004).

McKeen, H. D., Brennan, D. J., Hegarty, S., Lanigan, F., Jirstrom, K., Byrne, C., et al. (2011).

McKnight, T. E., Culbertson, C. T., Jacobson, S. C., & Ramsey, J. M. (2001).

Meehan, K. L., & Sadar, M. D. (2004). Quantitative profiling of LNCaP prostate cancer cells using isotope-coded affinity tags and mass spectrometry. *Proteomics, 4*(4), 1116-1134. Melse-Boonstra, A., Verhoef, P., West, C. E., van Rhijn, J. A., van Breemen, R. B., Lasaroms, J.

high mass accuracy. *Proceedings of the National Academy of Sciences of the United* 

Quantitative proteomic analysis of proteins released by neoplastic prostate

The emerging role of FK506-binding proteins as cancer biomarkers: a focus on

Electroosmotically induced hydraulic pumping with integrated electrodes on

J. P., et al. (2006). A dual-isotope-labeling method of studying the bioavailability of hexaglutamyl folic acid relative to that of monoglutamyl folic acid in humans by using multiple orally administered low doses. *American Journal of Clinical Nutrition,* 

measurements in proteomics. *Chemical Reviews, 107*(8), 3621-3653.

spectrometry. *Chemical Reviews, 107*(8), 3568-3584.

FKBPL. *Biochemical Society Transactions, 39*, 663-668.

microfluidic devices. *Analytical Chemistry, 73*(16), 4045-4049.

*States of America, 105*(47), 18132-18138.

epithelium. *Cancer Research, 64*(1), 347-355.

expression. *Br J Cancer*. Br J Cancer. 2012 Jan 3;106(1):157-65

*Biomarkers & Prevention, 14*(7), 1697-1702.

malignant tumor cell type. *Bmc Cancer, 11*.

*Molecular Cancer Therapeutics, 10*(3), 427-436.

3091.

*84*(5), 1128-1133.

selenomethionine supplementation in prostate cancer. *Cancer Epidemiology* 

Targeting surface nucleolin with multivalent HB-19 and related Nucant pseudopeptides results in distinct inhibitory mechanisms depending on the

al. (2011). Lipoprotein Lipase Links Dietary Fat to Solid Tumor Cell Proliferation.

Multiple reaction monitoring-based, multiplexed, absolute quantitation of 45

Identification of markers of prostate cancer progression using candidate gene

presence of disease-perturbed networks in prostate cancer cells by genomic and proteomic analyses: A systems approach to disease. *Cancer Research, 65*(8), 3081-


Hale, L. P., Price, D. T., Sanchez, L. M., Demark-Wahnefried, W., & Madden, J. F. (2001).

Hammarsten, J., & Hogstedt, B. (2002). Calculated fast-growing benign prostatic hyperplasia

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of Cancer: The Next Generation. *Cell,* 

Hanash, S. M., Pitteri, S. J., & Faca, V. M. (2008). Mining the plasma proteome for cancer

Hilario, M., & Kalousis, A. (2008). Approaches to dimensionality reduction in proteomic

Hildenbrand, Z. L., Molugu, S. K., Herrera, N., Ramirez, C., Xiao, C., & Bernal, R. A. (2011).

Hoeman, K. W., Lange, J. J., Roman, G. T., Higgins, D. A., & Culbertson, C. T. (2009).

Issaq, H. J., Xiao, Z., & Veenstra, T. D. (2007). Serum and plasma proteomics. *Chemical* 

Jaffe, J. D., Keshishian, H., Chang, B., Addona, T. A., Gillette, M. A., & Carr, S. A. (2008).

Jahnisch, K., Hessel, V., Lowe, H., & Baerns, M. (2004). Chemistry in microstructured

Jemal, A., Siegel, R., Xu, J. Q., & Ward, E. (2010). Cancer Statistics, 2010. *Ca-a Cancer Journal* 

Jeronimo, C., Henrique, R., Oliveira, J., Lobo, F., Pais, I., Teixeira, M. R., et al. (2004).

methylation in prostate cancer. *Journal of Clinical Pathology, 57*(8), 872-876. Jiang, W. G., & Ablin, R. J. (2011). Prostate transglutaminase: a unique transglutaminase and

Joyce, J. A. (2005). Therapeutic targeting of the tumor microenvironment. *Cancer Cell, 7*(6),

Khanna, C., Wan, X. L., Bose, S., Cassaday, R., Olomu, O., Mendoza, A., et al. (2004). The

Kim, C. J., Sakamoto, K., Tambe, Y., & Inoue, H. (2011). Opposite regulation of epithelial-to-

bladder cancer cells. *International Journal of Oncology, 38*(6), 1759-1766. Kim, J., Sun, P. Y., Lam, Y. W., Troncoso, P., Sabichi, A. L., Babaian, R. J., et al. (2005).

its role in prostate cancer. *Biomarkers in Medicine, 5*(3), 285-291.

gel chemistry on microfluidic devices. *Electrophoresis, 30*(18), 3160-3167. Hood, B. L., Darfler, M. M., Guiel, T. G., Furusato, B., Lucas, D. A., Ringeisen, B. R., et al.

biomarker studies. *Briefings in Bioinformatics, 9*(2), 102-118.

846-853.

*144*(5), 646-674.

*and Nephrology, 36*(5), 330-338.

biomarkers. *Nature, 452*(7187), 571-579.

Proteins. *Oncotarget, 2*(1-2), 43-58.

*Cellular Proteomics, 4*(11), 1741-1753.

reactors. *Angew Chem Int Ed Engl, 43*(4), 406-446.

*Reviews, 107*(8), 3601-3620.

*for Clinicians, 60*(5), 277-300.

*Nature Medicine, 10*(2), 182-186.

1952-1962.

513-520.

Zinc alpha-2-glycoprotein is expressed by malignant prostatic epithelium and may serve as a potential serum marker for prostate cancer. *Clinical Cancer Research, 7*(4),


Hsp90 can Accommodate the Simultaneous Binding of the FKBP52 and HOP

Electrokinetic trapping using titania nanoporous membranes fabricated using sol-

(2005). Proteomic analysis of formalin-fixed prostate cancer tissue. *Molecular &* 

Accurate inclusion mass screening: a bridge from unbiased discovery to targeted assay development for biomarker verification. *Molecular & Cellular Proteomics, 7*(10),

Aberrant cellular retinol binding protein 1 (CRBP1) gene expression and promoter

membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis.

mesenchymal transition and cell invasiveness by periostin between prostate and

Changes in serum proteomic patterns by presurgical alpha-tocopherol and L-

selenomethionine supplementation in prostate cancer. *Cancer Epidemiology Biomarkers & Prevention, 14*(7), 1697-1702.


The Discovery of Cancer Tissue Specific Proteins in Serum: Case Studies on Prostate Cancer 359

Rowland, J. G., Simon, J. W., Slabas, A. R., Robson, C. N., & Leung, H. Y. (2004).

Seymour, S. L., Shilov, I. V., Patel, A. A., Loboda, A., Tang, W. H., Keating, S. P., et al. (2006).

Shilov, I. V., Seymour, S. L., Patel, A. A., Loboda, A., Tang, W. H., Keating, S. P., et al. (2007).

Stoevesandt, O., & Taussig, M. J. (2007). Affinity reagent resources for human proteome

Sun, C. Y., Song, C., Ma, Z. C., Xu, K., Zhang, Y., Jin, H., et al. (2011). Periostin identified as a

Sun, C. Y., Zhao, X. J., Xu, K., Gong, J., Liu, W. W., Ding, W. H., et al. (2011). Periostin: a

Sytkowski, A. J., Gao, C., Feldman, L., & Chen, C. (2005). Human selenium binding protein-

Thompson, I. M., Ankerst, D. P., Chi, C., Lucia, M. S., Goodman, P. J., Crowley, J. J., et al.

Toki, K., Enokida, H., Kawakami, K., Chiyomaru, T., Tatarano, S., Yoshino, H., et al. (2010).

Tsavachidou, D., McDonnell, T. J., Wen, S. J., Wang, X. M., Vakar-Lopez, F., Pisters, L. L., et

Turteltaub, K. W., Davis, M. A., Burns-Naas, L. A., Lawton, M. P., Clark, A. M., & Reynolds,

van Bentem, S. D., Mentzen, W. I., de la Fuente, A., & Hirt, H. (2008). Towards functional

enrichment and separation. *Lab on a Chip, 11*(18), 3113-3120.

LNCaP prostate cancer cell line. *British Journal of Cancer, 91*, S38-S38. Rubakhin, S. S., Romanova, E. V., Nemes, P., & Sweedler, J. V. (2011). Profiling metabolites

and peptides in single cells. *Nature Methods, 8*(4), S20-S29. Sawyers, C. L. (2008). The cancer biomarker problem. *Nature, 452*(7187), 548-552.

mass spectra. *Molecular & Cellular Proteomics, 6*(9), 1638-1655.

detection: initiatives and perspectives. *Proteomics, 7*(16), 2738-2750.

*Molecular & Cellular Proteomics, 5*(10), S294-S294.

biopsy. *Proteome Science, 9*.

*Translational Medicine, 9*.

*Oncology, 23*(16), 852S-852S.

*Research, 17*(21), 6641-6645.

networks. *Proteomics, 8*(21), 4453-4465.

*294*(1), 66-70.

*37*(6), 1379-1388.

Quantitative proteomic analysis of androgen & anti-androgen responses in the

The application of the paragon algorithm to the study of protein modifications.

The paragon algorithm, a next generation search engine that uses sequence temperature values and feature probabilities to identify peptides from tandem

potential biomarker of prostate cancer by iTRAQ-proteomics analysis of prostate

promising target of therapeutical intervention for prostate cancer. *Journal of* 

1 (hSP56) inhibits anchorage-independent growth of PC-3 human prostate cancer cells and is down-regulated in primary human prostate tumor. *Journal of Clinical* 

(2005). Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/mL or lower. *Jama-Journal of the American Medical Association,* 

CpG hypermethylation of cellular retinol-binding protein 1 contributes to cell proliferation and migration in bladder cancer. *International Journal of Oncology,* 

al. (2009). Selenium and Vitamin E: Cell Type- and Intervention-Specific Tissue Effects in Prostate Cancer. *Journal of the National Cancer Institute, 101*(5), 306-320. Tsougeni, K., Zerefos, P., Tserepi, A., Vlahou, A., Garbis, S. D., & Gogolides, E. (2011).

TiO(2)-ZrO(2) affinity chromatography polymeric microchip for phosphopeptide

J. A. (2011). Identification and Elucidation of the Biology of Adverse Events: The Challenges of Safety Assessment and Translational Medicine. *Clinical Cancer* 

phosphoproteomics by mapping differential phosphorylation events in signaling


Menendez, J. A., & Lupu, R. (2007). Fatty acid synthase and the lipogenic phenotype in

Milad, M., Sullivan, W., Diehl, E., Altmann, M., Nordeen, S., Edwards, D. P., et al. (1995).

Miyoshi, Y., Ishiguro, H., Uemura, H., Fujinami, K., Miyamoto, H., Miyoshi, Y., et al. (2003).

Moretti, R. M., Mai, S., Marelli, M. M., Rizzi, F., Bettuzzi, S., & Limonta, P. (2011). Molecular

Mueller, M. M., & Fusenig, N. E. (2004). Friends or foes - Bipolar effects of the tumour

Mullins, C., Lucia, M. S., Hayward, S. W., Lee, J. Y., Levitt, J. M., Lin, V. K., et al. (2008). A

Nelson, W. G., DeMarzo, A. M., DeWeese, T. L., & Isaacs, W. B. (2005). The molecular pathogenesis of human prostate cancer. *Hormonal Carcinogenesis Iv*, 34-44. Nilsson, T., Mann, M., Aebersold, R., Yates, J. R., Bairoch, A., & Bergeron, J. J. M. (2010).

Oh, K. S., Khan, S. G., Jaspers, N. G. J., Raams, A., Ueda, T., Lehmann, A., et al. (2006).

Okuda, M., Horn, H. F., Tarapore, P., Tokuyama, Y., Smulian, A. G., Chan, P. K., et al.

Ong, S. E., & Mann, M. (2005). Mass spectrometry-based proteomics turns quantitative.

Papayannopoulos, I. A. (1995). The Interpretation of Collision-Induced Dissociation Tandem

Pfeffer, U., Tosetti, F., Ferrari, N., Vene, R., Benelli, R., Morini, M., et al. (2002).

Planche, A., Bacac, M., Provero, P., Fusco, C., Delorenzi, M., Stehle, J. C., et al. (2011).

Rahbar, A., Rivers, R., Boja, E., Kinsinger, C., Mesri, M., Hiltke, T., et al. (2011). Realizing

Rissin, D. M., Kan, C. W., Campbell, T. G., Howes, S. C., Fournier, D. R., Song, L., et al.

proteins at subfemtomolar concentrations. *Nat Biotechnol, 28*(6), 595-599.

agents. *Cancer Epidemiology Biomarkers & Prevention, 11*(10), 1235S-1235S. Pichler, P., Kocher, T., Holzmann, J., Mohring, T., Ammerer, G., & Mechtler, K. (2011).

Mass-Spectra of Peptides. *Mass Spectrometry Reviews, 14*(1), 49-73.

in an Orbitrap HCD Cell. *Analytical Chemistry, 83*(4), 1469-1474.

Interaction of the Progesterone-Receptor with Binding-Proteins for Fk506 and

Expression of AR associated protein 55 (ARA55) and androgen receptor in prostate

mechanisms of the antimetastatic activity of nuclear clusterin in prostate cancer

comprehensive approach toward novel serum biomarkers for benign prostatic

Mass spectrometry in high-throughput proteomics: ready for the big time. *Nature* 

Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): Xeroderma pigmentosum without and with Cockayne syndrome. *Human Mutation, 27*(11),

(2000). Nucleophosmin/B23 is a target of CDK2/Cyclin E in centrosome

Angioprevention: Anti-angiogenesis as a critical target for cancer chemopreventive

Improved Precision of iTRAQ and TMT Quantification by an Axial Extraction Field

Identification of Prognostic Molecular Features in the Reactive Stroma of Human

individualized medicine: the road to translating proteomics from the laboratory to

(2010). Single-molecule enzyme-linked immunosorbent assay detects serum

cancer pathogenesis. *Nature Reviews Cancer, 7*(10), 763-777.

Cyclosporine-A. *Molecular Endocrinology, 9*(7), 838-847.

cells. *International Journal of Oncology, 39*(1), 225-234.

stroma in cancer. *Nature Reviews Cancer, 4*(11), 839-849.

hyperplasia: the MPSA Consortium. *J Urol, 179*(4), 1243-1256.

cancer. *Prostate, 56*(4), 280-286.

*Methods, 7*(9), 681-685.

duplication. *Cell, 103*(1), 127-140.

*Nature Chemical Biology, 1*(5), 252-262.

Breast and Prostate Cancer. *Plos One, 6*(5).

the clinic. *Personalized Medicine, 8*(1), 45-57.

1092-1103.


**1. Introduction** 

**1.1.1 Proteomics** 

**1.1.2 Serum proteomics** 

**1.1 Concept** 

**17** 

*China* 

**Serum Peptidomics** 

Weirong Guo2 and Jian Yuan1

*2Bioyong (Beijing) Technologies Limited, Beijing,* 

Kaihua Wei1, Qingwei Ma2, Yunbo Sun1, Xiaoming Zhou1,

The performer of life functions is the dynamically-changing protein, rather than the relativelystatic gene. Accordingly, the study of protein is of practical significance in the explication of vital phenomena, especially in the revelation of onset, deterioration and outcome of human diseases, which is also a driving force for the emergence of proteomics. Wilkins and Williams (Wasinger VC. et al, 1995) initiated the study of proteomics by putting forward the concept of proteomics for the first time. The proteome is the set of expressed proteins in a given type of cells, tissues or an organism at a given time under defined conditions. Proteomics is the largescale study of proteomes, to discover composition and expression of proteins in organism, to understand interactions between proteins and explore functions of proteins and laws of vital activities of cells. It covers expression proteomics, functional proteomics and cell-localization proteomics etc. The proteomics technologies has provided a new tool for studying the

When proteomics comes to the clinical applications, it mainly refers to serum proteomics. The features of serum proteome research: firstly, it is easily to access samples, which means that it is able to meet the research requirements and easy to standardize; secondly, the dynamic variation in serum proteins is capable to reflect the pathological changing state of human organs; this is of far-reaching importance for disease diagnosis and curative effect monitoring. Human Proteome Organization (HUPO) brought the human plasma/serum proteome plan under the first-phase of the human proteome plans, which is showing the

Taking all proteins expressed in the serum of selected target clusters as the object, the serum proteomics, based on the normal protein expression profiles, aims to look for the differential proteins and define disease-associated proteins, the structures and functions of which will further be studied. In the hope of presenting a new approach for studying the pathological and physiological mechanisms of severe diseases, specific protein markers are expected to

significance of studying serum proteomics for healthy and sick states of human.

biomarkers, pathogeny mechanism, diagnostic methods of diseases.

*1State Key Lab of Proteomics, Beijing Proteome Research Center,* 

