前列腺体作为前列腺癌检测的诊断工具
循环前列腺体的定量和纯化作为前列腺癌检测的诊断工具
Prostate cancer is the most frequently diagnosed cancer among men over 50 years old in Western societies, with an incidence that is steadily increasing in most countries. The current, most commonly used biomarker for prostate cancer is prostate specific antigen (PSA), which has well known limitations in accuracy and requires additional testing. However, prostate cancer cells secrete exosomes, also known as prostasomes, which are only detectable in the blood of prostate cancer patients. The presence of prostasomes in the blood is in itself a prostate cancer diagnosis. However, the assay that has been designed for the purification of prostasomes requires additional testing for evaluating its robustness and usefulness in the clinical setting. Additionally, the evaluation of the cargo of the purified prostasomes may provide more information on the nature of the prostate cancer, which may help develop a molecular assay for a prostate cancer liquid biopsy rather than a tissue biopsy. Therefore, the purpose of this study is two-fold: a validation phase where the purification of prostasomes will be tested on plasma collected from prostate cancer patients and a molecular testing phase where the contents of the purified prostasomes will be evaluated on their ability to determine the grade of the prostate tumors.
We will collaborate with Dr. Masood Kamali-Moghaddam at the Uppsala University (Department of Immunology, Genetics and Pathology) for molecular assay processing.
研究概览
研究类型
注册 (估计的)
联系人和位置
学习地点
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New Jersey
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Hackensack、New Jersey、美国、07601
- Hackensack University Medical Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
All male patients with elevated PSA and suspected for prostate cancer or patients with diagnosed prostate cancer but prior to treatment will be invited to participate. Depending on the results from the diagnostic MRI-guided biopsy, participants will be assigned to either the control cohort (if biopsy is negative) or the patient cohort (if biopsy is positive).
描述
Inclusion Criteria:
- Male
- With elevated PSA or patients with diagnosed prostate cancer
- 18 years and older
- Willingness to participate in the study and compliance with protocol requirements
- Have not received any type of treatment for prostate cancer
Exclusion Criteria:
- Patients with confirmed or suspected prostate cancer that have already received any type of treatment
- Patients with another primary cancer within the past five years of prostate cancer diagnosis. However, superficial skin cancers such as basal cell or squamous cell cancers would not exclude a patient.
学习计划
研究是如何设计的？
设计细节
- 观测模型：COHORT
- 时间观点：PROSPECTIVE
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
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Patient population
Male individuals with elevated PSA and a positive MRI-driven biopsy AND male individuals with diagnosed prostate cancer (but prior to any treatment) |
Whole blood will be collected and processed within 2 hours. Samples will be brought to Hackensack University Medical Center and will be centrifuged. The plasma samples will be tested for presence of prostasomes using the ExoPLA (Exosome in situ Proximity Ligation Assay) assay and the prostasomes will be purified for further miRNA sequencing. |
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Control Population
Male individuals with elevated PSA and a negative MRI-driven biopsy |
Whole blood will be collected and processed within 2 hours. Samples will be brought to Hackensack University Medical Center and will be centrifuged. The plasma samples will be tested for presence of prostasomes using the ExoPLA (Exosome in situ Proximity Ligation Assay) assay and the prostasomes will be purified for further miRNA sequencing. |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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sensitivity of the prostasome purification methodology
大体时间：through study completion - up to 24 months
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true positive rate of the prostasomes purification methodology using the prostasome detection results for each of the patient specimens (cases and controls) |
through study completion - up to 24 months
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specificity of the prostasome purification methodology
大体时间：through study completion - up to 24 months
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true negative rate of the prostasomes purification methodology using the prostasome detection results for each of the patient specimens (cases and controls) |
through study completion - up to 24 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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疾病进展时间（仅限患者队列）
大体时间：长达 24 个月
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长达 24 个月
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疾病复发时间（仅限患者队列）
大体时间：长达 24 个月
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长达 24 个月
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总生存期（仅在患者队列中）
大体时间：长达 24 个月
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长达 24 个月
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Quantification of the miRNA expression profiles of the purified protostomes both before and after treatment (in patients cohort only)
大体时间：through study completion - up to 24 months
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identify the top 20 most frequently expressed miRNA markers and their level of expression in each of the case patient specimens |
through study completion - up to 24 months
|
合作者和调查者
出版物和有用的链接
一般刊物
- 1. Gomella LG, Johannes J, Trabulsi EJ. Current prostate cancer treatments: Effect on quality of life. Urology. 2009;73(5, Suppl): S28-S35. 2. Network, N.C.C. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer, Version 2.2017. [cited 2017 May 31];2017 Available from: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf. 3. Pienta KJ. Critical appraisal of prostate-specific antigen in prostate cancer screening: 20 years later. Urology. 2009;73(5, Suppl):S11-S20. 4. Stamey TA, et al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med. 1987;317:909-916. 5. Catalona WJ. Management of cancer of the prostate. N Engl J Med. 1994;331:996-1004. 6. Harvey P, et al. A systematic review of the diagnostic accuracy of prostate specific antigen. BMC Urol. 2009;9:14. 7. Cramer SD, et al. Association between genetic polymorphisms in the prostate-specific antigen gene promoter and serum prostate-specific antigen levels. J Natl Cancer Inst. 2003;95:1044-1053.
- 8. Inal JM, Kosgodage U, Azam S, Stratton D, Antwi-Baffour S, Lange S. Blood/plasma secretome and microvesicles. Biochim Biophys Acta. 2013;1834(11):2317-25. 9. Ronquist G, Brody I, Gottfries A, Stegmayr B. An Mg2+ and Ca2+-stimulated adenosine triphosphatase in human prostatic fluid-part II. Andrologia. 1978;10:427-433. 10. Ronquist G, Brody I, Gottfries A, Stegmayr B. An Mg2+ and Ca2+-stimulated adenosine triphosphatase in human prostatic fluid: Part I. Andrologia. 1978;10:261-272. 11. Ronquist G, Hedström M. Restoration of detergent-inactivated adenosine triphosphatase activity of human prostatic fluid with concanavalin A. Biochim Biophys Acta. 1977;483:483-486. 12. Minciacchi VR, Zijlstra A, Rubin MA, Di Vizio D. Extracellular vesicles for liquid biopsy in prostate cancer: where are we and where are we headed? Prostate Cancer Prostatic Dis. 2017;20(3):251-258. 13. Poliakov A, Spilman M, Dokland T, Amling CL, Mobley JA. Structural heterogeneity and protein composition of exosome-like vesicles (prostasomes) in human semen. Prostate. 2009;69:159-167. 14. Utleg AG, et al. Proteomic analysis of human prostasomes. Prostate. 2003;56:150-161. 15. Carlsson L, et al. Characteristics of human prostasomes isolated from three different sources. Prostate. 2003;54:322-330.
- 16. Carlsson L, Ronquist G, Eliasson R, Egberg N, Larsson A. Flow cytometric technique for determination of prostasomal quantity, size and expression of CD10, CD13, CD26 and CD59 in human seminal plasma. Int J Androl. 2006;29:331-338. 17. Fernández JA, Heeb MJ, Radtke KP, Griffin JH. Potent blood coagulant activity of human semen due to prostasome-bound tissue factor. Biol Reprod. 1997;56:757-763. 18. Fabiani R, Johansson L, Lundkvist O, Ronquist G. Enhanced recruitment of motile spermatozoa by prostasome inclusion in swim-up medium. Hum Reprod. 1994;9:1485-1489. 19. Carlsson L, Påhlson C, Bergquist M, Ronquist G, Stridsberg M. Antibacterial activity of human prostasomes. Prostate. 2000;44:279-286. 20. Rooney IA, et al. Physiologic relevance of the membrane attack complex inhibitory protein CD59 in human seminal plasma: CD59 is present on extracellular organelles (prostasomes), binds cell membranes, and inhibits complement-mediated lysis. J Exp Med. 1993;177:1409-1420. 21. Saez F, Motta C, Boucher D, Grizard G. Antioxidant capacity of prostasomes in human semen. Mol Hum Reprod. 1998;4:667-672. 22. Skibinski G, Kelly RW, Harkiss D, James K. Immunosuppression by human seminal plasma-extracellular organelles (prostasomes) modulate activity of phagocytic cells. Am J Reprod Immunol. 1992;28:97-103.
- 23. Floryk D, Tollaksen SL, Giometti CS, Huberman E. Differentiation of human prostate cancer PC-3 cells induced by inhibitors of inosine 5'-monophosphate dehydrogenase. Cancer Res. 2004;64:9049-9056. 24. Nilsson BO, Egevad L, Jin M, Ronquist G, Busch C. Distribution of prostasomes in neoplastic epithelial prostate cells. Prostate. 1999;39:36-40. 25. Sahlén G, et al. Prostasomes are secreted from poorly differentiated cells of prostate cancer metastases. Prostate. 2004;61:291-297. 26. Fredriksson S, et al. Protein detection using proximity-dependent DNA ligation assays. Nat Biotechnol. 2002;20:473-477. 27. Tavoosidana G, Ronquist G, Darmanis S, Yan J, Carlsson L, Wu D, Conze T, Ek P, Semjonow A, Eltze E, Larsson A, Landegren UD, Kamali-Moghaddam M. Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8809-14. 28. Löf L, Ebai T, Dubois L, Wik L, Ronquist KG, Nolander O, Lundin E, Söderberg O, Landegren U, Kamali-Moghaddam M. Detecting individual extracellular vesicles using a multicolor in situ proximity ligation assay with flow cytometric readout. Sci Rep. 2016; 6:34358. 29. Loudig O, Wang T, Ye K, Lin J, Wang Y, Ramnauth A, Liu C, Stark A, Chitale D, Greenlee R, Multerer D, Honda S, Daida Y, Spencer Feigelson H, Glass A, Couch FJ, Rohan T, Ben-Dov IZ. Evaluation and Adaptation of a Laboratory-Based cDNA Library Preparation Protocol for Retrospective Sequencing of Archived MicroRNAs from up to 35-Year-Old Clinical FFPE Specimens. Int J Mol Sci. 2017; 18(3). pii: E627. 30. Loudig O, Liu C, Rohan T, and Ben-Dov IZ. Retrospective MicroRNA Sequencing: Complementary DNA Library Preparation Protocol Using Formalin-fixed Paraffin-embedded RNA Specimens. Journal of Visualized Experiments, 2018.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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