Abstract
Introduction
Proteomic biomarkers may be useful for monitoring therapeutic response and to triage cancer patients to best therapy.
Objectives
In this review, we highlight the importance of specimen acquisition, preparation and analysis in radiotherapy proteomic studies. We also discuss practical approaches for the design and execution of clinical proteomic studies using our recent experience based on specimens accrued during prostate cancer radiation therapy.
Discussion and Conclusions
Numerous proteomic methods are being employed, including high-throughput mass spectrometry and immunoassays, and using solid tissues, blood and urine for analysis. Given the potential complexity of cytokine and other protein responses, there is a need to assess proteomic signatures within serial samples as longitudinal studies during a course of fractionated radiotherapy (RT).
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Abbreviations
- RT:
-
radiation therapy
- PCa:
-
prostate cancer
- PSA:
-
prostate specific antigen
- TNM:
-
UICC Tumor stage (TumorNodeMetastasis)
- MS:
-
mass spectrometry
- IMRT:
-
intensity-modulated radiation therapy
- IGRT:
-
image-guided radiation therapy
- MRM:
-
multiple reaction monitoring
References
Kingsmore, S. F. (2006). Multiplexed protein measurement: Technology and applications of protein and antibody arrays. Nature Reviews Drug Discovery, 4, 310–320.
Diamandis, E. P. (2004). Mass spectrometry as a diagnostic and cancer biomarker discovery tool. Molecular and Cellular Proteomics, 3, 367–378.
Tricoli, J. V., Schoenfeldt, M., & Conley, B. A. (2004). Detection of prostate cancer and predicting progression. Clinical Cancer Research, 10, 3943–3953.
Becker, C., Piironen, T., Pettersson, K., Bjork, T., Wojno, K., Oesterling, J., et al. (2000). Discrimination of men with prostate cancer from those with benign disease by measurements of human glandular kallikrein 2 (HK2) in serum. Journal of Urology, 163, 311–316.
Catalona, W., Beiser, J., & Smith, D. (1997). Serum free prostate specific antigen and prostate specific antigen density measurements for predicting cancer in men with prior negative prostatic biopsies. Journal of Urology, 158, 2162–2167.
Catalona, W., Richie, J., deKernion, J., Ahmann, F., Ratliff, T., Dalkin, B., et al. (1994). Comparison of prostate specific antigen concentration versus prostate specific antigen density in the early detection of prostate cancer: Receiver operating characteristic curves. Journal of Urology, 152, 2031–2036.
Steuber, T., Helo, P., & Lilja, H. (2007). Circulating biomarkers for prostate cancer. World Journal of Urology, 25, 111–119.
Carter, D., Douglass, J., Cornellison, C., Retter, M., Johnson, J., Bennington, A., et al. (2002). Purification and characterization of the mammaglobin/lipophilin B complex, a promising diagnostic marker for breast cancer. Biochemistry, 41, 6714–6722.
Rosty, C., Christa, L., Kuzdzal, S., Baldwin, W., Zahurak, M., Carnot, F., et al. (2002). Identification of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein I as a biomarker for pancreatic ductal adenocarcinoma by protein biochip technology. Cancer Research, 62, 1868–1875.
Petricoin, E. F., & Liotta, L. A. (2003). Proteomic approaches in cancer risk and response assessment. Trends in Molecular Medicine, 10, 59–64.
Veenstra, T., Prieto, D., & Conrads, T. (2004). Proteomic patterns for early cancer detection. Drug Discovery Today, 9, 889–897.
Nichol, A. M., Wardge, P., & Bristow, R. G. (2005). Optimal treatment of intermediate-risk prostate carcinoma with radiotherapy. Cancer, 104, 891–905.
Merrick, G., Butler, W., Wallner, K., Galbreath, R., & Anderson, R. (2002). Prostate-specific antigen spikes after permanent prostate brachytherapy. International Journal of Radiation Oncology Biology and Physics, 54, 450–456.
Borgono, C. A., & Diamandis, E. P. (2004). The emerging roles of human tissue kallikreins in cancer. Nature Reviews Cancer, 4, 876–890.
Laxman, B., Morris, D. S., Yu, J., Siddiqui, J., Cao, J., Mehra, R., et al. (2008). A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer. Cancer Research, 68, 645–649.
Pavy, J., Denekamp, J., Letschert, J., Littbrand, B., Mornex, F., Bernier, J., et al. (1995). EORTC Late Effects Working Group. Late effect toxicity scoring: The SOMA scale. Radiotherapy and Oncology, 35, 11–15.
Faulhaber, O., & Bristow, R. G. (2005). Basis of cell kill following clinical radiotherapy. In M. Sluyser (Ed.), Application of apoptosis to cancer treatment (pp. 293–320). Berlin: Springer.
Hagan, M., Yacoub, A., & Dent, P. (2004). Ionizing radiation causes a dose-dependent release of transforming growth factor alpha in vitro from irradiated xenografts and during palliative treatment of hormone-refractory prostate carcinoma. Clinical Cancer Research, 10, 5724–5731.
Borgono, C. A., & Diamandis, E. P. (2004). The emerging roles of human tissue kallikreins in cancer. Nature Review Cancer, 4, 876–890.
McLean, M., Panzarella, T., Warde, P., Gospodarowicz, M., Duncan, W., Catton, C., et al. (1997). Prostate specific antigen levels during radical radiation therapy and the prediction of outcome in localized carcinoma of the prostate. Clinical Oncology, 9, 226–233.
Petricoin, E. F., Ardekani, A. M., Hitt, B. A., Levine, P. J., Fusaro, V. A., Steinberg, S. M., et al. (2002). Use of proteomic patterns in serum to identify ovarian cancer. Lancet, 359, 572–577.
Rubin, P., Johnston, C. J., Williams, J. P., McDonald, S., & Finkelstein, J. N. (1995). A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. International Journal of Radiation Oncology Biology and Physics, 33, 99–109.
Petricoin, E., Ardekani, A., Hitt, B., Levine, P., Fusaro, V., Steinberg, S., et al. (2002). Use of proteomic patterns in serum to identify ovarian cancer. Lancet, 359, 572–577.
Liu, X., Shen, J., Li, Z., Yan, L., & Gu, J. (2006). A serum proteomic pattern for the detection of colorectal adenocarcinoma using surface enhanced laser desorption and ionization mass spectrometry. Cancer Investigations, 24, 747–753.
Li, J., White, N., Zhang, Z., Rosenzweig, J., Mengold, L. A., Partin, A. W., et al. (2004). Detection of prostate cancer using serum proteomics pattern in a histologically confirmed population. The Journal of Urology, 171, 1782–1787.
Petricoin, E. F., Ornstein, D. K., Paweletz, C. P., Ardekani, A., Hackett, P. S., Hitt, B. A., et al. (2002). Serum proteomic patterns for detection of prostate cancer. Journal of the National Cancer Institute, 94, 1576.
Gao, W.-M., Kuick, R., Orchekowski, R. P., Misek, D. E., Qiu, J., Greenberg, A.K., et al. (2005). Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis. BMC Cancer, 5, 110.
Alexander, H., Stegner, A., Wagner-Mann, C., Bois, G. D., Alexander, S., & Sauter, E. (2004). Proteomic analysis to identify breast cancer biomarkers in nipple aspirate fluid. Clinical Cancer Research, 10, 7500–7510.
Rui, Z., Jian-Guo, J., Yuan-Peng, T., Hai, P., & Bing-Gen, R. (2003). Use of serological proteomic methods to find biomarkers associated with breast cancer. Proteomics, 3, 433–439.
Gokhale, A. S., Haddad, R. I., Cavacini, L. A., Wirth, L., Weeks, L., Hallar, M., et al. (2005). Serum concentrations of interleukin-8, vascular endothelial growth factor, and epidermal growth factor receptor in patients with squamous cell cancer of the head and neck. Oral Oncology, 41, 70–76.
Gridley, D., Loredo, L., Slater, J., Archambeau, J., Bedros, A., Andres, M., et al. (1998). Pilot evaluation of cytokine levels in patients undergoing radiotherapy for brain tumor. Cancer Detection and Prevention, 22, 20–29.
Hotte, S. J., Wingquist, E. W., Stitt, L., Wilson, S. M., & Chambers, A. F. (2002). Plasma osteopontin: Associations with survival and metastasis to bone in men with hormone-refractory prostate carcinoma. Cancer, 95, 506–512.
Bramwell, V. H., Doig, G. S., Tuck, A. B., Wilson, S. M., Tonkin, K. S., Tomiak, A., et al. (2006). Serial plasma osteopontin levels have prognostic value in metastatic breast cancer. Clinical Cancer Research, 12, 3337–3343.
Menard, C., Johann, D., Lowenthal, M., Muanza, T., Sproull, M., Ross, S., et al. (2006). Discovering clinical biomarkers of ionizing radiation exposure with serum proteomic analysis. Cancer Research, 66, 1844–1850.
Allal, A. S., Kahne, T., Reverdin, A. K., Lippert, H., Schlegel, W., & Reymond, M.-A. (2004). Radioresistance-related proteins in rectal caner. Proteomics, 4, 2261–2269.
Allen, C., Duffy, S., Teknos, T., Islam, M., Chen, Z., Albert, P. S., et al. (2007). Nuclear factor-kB-related serum factors as longitudinal biomarkers of response and survival in advanced oropharyngeal carcinoma. Clinical Cancer Research, 13, 3182–3190.
Druzgal, C. H., Chen, Z., Yeh, N. T., Thomas, G. R., Ondrey, F. G., Duffey, D. C., et al. (2005). A pilot study of longitudinal serum cytokine and angiogenesis factor levels as markers of therapeutic response and survival in patients with head and neck squamous cell carcinoma. Head & Neck, 27, 771–784.
Teknos, T. N., Cox, C., Yoo, S., Chepeha, D. B., Wolf, G. T., Bradford, C. R., et al. (2002). Elevated serum vascular endothelial growth factor and decreased survival in advanced laryngeal carcinoma. Head & Neck, 24, 1004–1011.
Kovacs, C., Daly, B., Evans, M., Johnke, R., Lee, T., Karlsson, U., et al. (2003). Cytokine profiles in patients receiving wide-field + prostate boost radiotherapy (xRT) for adenocarcinoma of the prostate. Cytokine, 23, 151–163.
Turesson, I., Bernefors, R., Book, M., Flogegard, M., Hermansson, I., Johansson, K.-A., et al. (2001). Normal tissue response to low doses of radiotherapy assessed by molecular markers: A study of skin in patients treated for prostate cancer. Acta Oncologica, 40, 941–951.
Ward, D., Cheng, Y., N’Kontchou, G., Thar, T., Barget, N., Wei, W., et al. (2006). Preclinical and post-treatment changes in the HCC-associated serum proteome. British Journal of Cancer, 95, 1379–1383.
Wickremesekera, J. K., Chen, W., Cannan, R. J., & Stubbs, R. S. (2001). Serum proinflammatory cytokine response in patients with advanced liver tumors following selective internal radiation therapy (SIRT) with 90yttrium microspheres. International Journal of Radiation Oncology Biology and Physics, 49, 1015–1021.
Anscher, M., Murase, T., Prescott, D., Marks, L., Reisenbichler, H., Bentel, G., et al. (1994). Changes in plasma TGF beta levels during pulmonary radiotherapy as a predictor of the risk of developing radiation pneumonitis. International Journal of Radiation Oncology Biology and Physics, 30, 671–676.
Chen, Y., Williams, J., Ding, I., Hernady, E., Liu, W., Smudzin, T., et al. (2002). Radiation pneumonitis and early circulatory cytokine markers. Seminars in Radiation Oncology, 12, 26–33.
Hara, R., Itami, J., Komiyama, T., Katoh, D., & Kondo, T. (2004). Serum levels of KL-6 for predicting the occurrence of radiation pneumonitis after stereotactic radiotherapy for lung tumors. Chest, 125, 340–344.
Downes, M., Byrne, J., Dunn, M., Fitzpatrick, J., Watson, R., & Pennington, S. (2006). Application of proteomic strategies to the identification of urinary biomarkers for prostate cancer: A review. Biomarkers, 11, 406–416.
Petricoin, E., & Liotta, L. (2004). Proteomic approaches in cancer risk and response assessment. Trends in Molecular Medicine, 10, 59–64.
Baggerly, K. A., Morris, J. S., & Coombes, K. R. (2004). Reproducibility of SELDI-TOF protein patterns in serum: Comparing datasets from different experiments. Bioinformatics, 20, 777–785.
Constans, A. (2006). Serum proteomics scrutinized. The Scientist, 20, 65–67.
Smith, P. C., Hobisch, A., Lin, D.-L., Culig, Z., & Keller, E. T. (2001). Interleukin-6 and prostate cancer progression. Cytokine and Growth Factor Reviews, 12, 33–40.
Shariat, S., Karam, J., & Roehrborn, C. (2007). Blood biomarkers for prostate cancer detection and prognosis. Future Oncology, 3, 449–461.
Shaw, J., & Diamandis, E. P. (2007). Distribution of 15 human kallikreins in tissues and biological fluids. Clinical Chemistry, 53, 1423–1432.
Veveris-Lowe, T., Kruger, S., Walsh, T., Gardiner, R., & Clements, J. (2007). Seminal fluid characterization for male fertility and prostate cancer: Kallikrein-related serine proteases and whole proteome approaches. Seminars in Thrombosis and Hemostasis, 33, 87–99.
Holland, N. T., Smith, M. T., Eskenazi, B., & Bastaki, M. (2003). Biological sample collection and processing for molecular epidemiological studies. Mutation Research, 543, 217–234.
Vaught, J. B. (2006). Blood collection, shipment, processing, and storage. Cancer Epidemiology Biomarkers & Prevention, 15, 1582–1584.
Leroux-Roels, G., Offner, F., Phillipe, J., & Vermeulen, A. (1988). Influence of blood-collecting systems on concentrations of tumor necrosis factor in serum and plasma. Clinical Chemistry, 34, 2373–2374.
Riches, P., Gooding, R., Millar, B. C., & Rowbottom, A. W. (1992). Influence of collection and separation of blood samples on plasma IL-1, IL-6, and TNF-a concentrations. Journal of Immunological Methods, 153, 125–131.
House, R. V. (2001). Cytokine measurement techniques for assessing hypersensitivity. Toxicology, 158, 51–58.
Bautista, D., Saad, Z., Chambers, A., Tonkin, K., O'Malley, F., Singhal, H., et al. (1996). Quantification of osteopontin in human plasma with an ELISA: Basal levels in pre- and postmenopausal women. Clinical Biochemistry, 29, 231–239.
Thavasu, P., Longhurst, S., Joel, S., Slevin, M., & Balkwill, F. (1992). Measureing cytokine levels in blood: Importance of anticoagulants, processing and storage conditions. Journal of Immunological Methods, 153, 115–124.
Cohen, E. P., and Lemann Jr., J. (1991). The role of the laboratory in evaluation of kidney function. Clinical Chemistry, 37, 785–796.
Pisitkun, T., Johnstone, R., & Knepper, M. A. (2006). Discovery of urinary biomarkers. Molecular and Cellular Proteomics, 5, 1760–1771.
Wheeler, T. N., Blackhurst, D., Dellinger, E., & Ramsey, P. (2007). Usage of spot urine protein to creatinine ratios in the evaluation of preeclampsia. American Journal of Obstetrics and Gynecology, 196, 465.e461–465.e464.
Acknowledgements
Supported by grants from National Cancer Institute of Canada, the Terry Fox Foundation and the Ontario Institute for Cancer Research (OICR-OCRN) to RGB and KE. EC is supported by a Matthews Family Scholarship in Radiation Therapy, a CIHR Strategic Training Fellowship in Radiation Medicine Research and an Ontario Graduate Scholarship. RGB is a Canadian Cancer Society Research Scientist.
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Christensen, E., Evans, K.R., Ménard, C. et al. Practical approaches to proteomic biomarkers within prostate cancer radiotherapy trials. Cancer Metastasis Rev 27, 375–385 (2008). https://doi.org/10.1007/s10555-008-9139-6
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DOI: https://doi.org/10.1007/s10555-008-9139-6