Urinary aHGF, IGFBP3 and OPN as diagnostic and prognostic biomarkers for prostate cancer.

AIM Serum PSA screening for prostate cancer (PCa) is controversial. Here, we identify three urinary biomarkers - aHGF, IGFBP3 and OPN - for PCa screening and prognostication. METHODS Urinary aHGF, OPN and IGFBP3 from healthy men (n = 19) and men with localized (n = 65) and metastatic (n = 36) PCa were quantified via ELISA. Mann-Whitney nonparametric t-test and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analyses were used to analyze associations. RESULTS Mean aHGF and IGFBP3 levels were significantly elevated in PCa patients versus controls (p = 0.0006 and p = 0.0012, respectively), and the area under the curve of the receiver operating characteristic curve (indicator of diagnostic accuracy) for aHGF and IGFBP3 was 0.75 and 0.74, respectively. OPN levels were significantly higher in metastatic groups (p = 0.0060) versus localized and controls (area under the curve = 0.68). CONCLUSION Urinary aHGF and IGFBP3 exhibit the capacity for diagnostic discrimination for PCa, whereas OPN may indicate presence of metastatic disease.

[1]  K. Camphausen,et al.  Correlation of Plasma FL Expression with Bone Marrow Irradiation Dose , 2013, PloS one.

[2]  C. Ménard,et al.  Plasma osteopontin as a biomarker of prostate cancer aggression: relationship to risk category and treatment response , 2012, British Journal of Cancer.

[3]  K. Taranta-Janusz,et al.  Urinary OPN excretion in children with glomerular proteinuria. , 2011, Advances in medical sciences.

[4]  Nallasivam Palanisamy,et al.  Urine TMPRSS2:ERG Fusion Transcript Stratifies Prostate Cancer Risk in Men with Elevated Serum PSA , 2011, Science Translational Medicine.

[5]  A. Villers,et al.  Abnormal Expression of the ERG Transcription Factor in Prostate Cancer Cells Activates Osteopontin , 2011, Molecular Cancer Research.

[6]  R. William G. Watson,et al.  Biomarker research in prostate cancer—towards utility, not futility , 2011, Nature Reviews Urology.

[7]  P. Albertsen,et al.  Use and assessment of PSA in prostate cancer. , 2011, The Medical clinics of North America.

[8]  J. Tosoian,et al.  PSA and Beyond: The Past, Present, and Future of Investigative Biomarkers for Prostate Cancer , 2010, TheScientificWorldJournal.

[9]  Zhaohui S. Qin,et al.  An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression. , 2010, Cancer cell.

[10]  A. Chambers,et al.  Extracellular matrix: a gatekeeper in the transition from dormancy to metastatic growth. , 2010, European journal of cancer.

[11]  B. Robertson,et al.  Osteopontin induces beta-catenin signaling through activation of Akt in prostate cancer cells. , 2010, Experimental cell research.

[12]  K. Iczkowski Cell adhesion molecule CD44: its functional roles in prostate cancer. , 2010, American journal of translational research.

[13]  Pär Stattin,et al.  Prostate specific antigen for early detection of prostate cancer: longitudinal study , 2009, BMJ : British Medical Journal.

[14]  D. Feldman,et al.  Unraveling insulin-like growth factor binding protein-3 actions in human disease. , 2009, Endocrine reviews.

[15]  K. Camphausen,et al.  Urine Analysis and Protein Networking Identify Met as a Marker of Metastatic Prostate Cancer , 2009, Clinical Cancer Research.

[16]  Angela Mariotto,et al.  Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. , 2009, Journal of the National Cancer Institute.

[17]  Y. Fujiuchi,et al.  The Prostate 69 : 346 ^ 351 ( 2009 ) SerumActiveHepatocyteGrowth Factor ( AHGF ) in Benign ProstaticDisease and ProstateCancer , 2009 .

[18]  K. Huo,et al.  IGFBP3 polymorphisms and risk of cancer: a meta-analysis , 2009, Molecular Biology Reports.

[19]  C. Roehrborn,et al.  Predictive Value of Plasma Hepatocyte Growth Factor/Scatter Factor Levels in Patients with Clinically Localized Prostate Cancer , 2008, Clinical Cancer Research.

[20]  M. Kosanović,et al.  Fibronectin Pattern in Benign Hyperplasia and Cancer of the Prostate , 2008, Disease markers.

[21]  K. Camphausen,et al.  Non-patient related variables affecting levels of vascular endothelial growth factor in urine biospecimens , 2008, Journal of cellular and molecular medicine.

[22]  P. Marker Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells , 2007 .

[23]  R. Eeles,et al.  Diversity of TMPRSS2-ERG fusion transcripts in the human prostate , 2007, Oncogene.

[24]  L. Holmberg,et al.  Prostate-specific antigen levels as a predictor of lethal prostate cancer. , 2007, Journal of the National Cancer Institute.

[25]  S. Loening,et al.  Plasma osteopontin in comparison with bone markers as indicator of bone metastasis and survival outcome in patients with prostate cancer , 2007, The Prostate.

[26]  M. Dunn,et al.  Urinary markers for prostate cancer , 2007, BJU international.

[27]  R. Millikan,et al.  Prostate cancer progression in the presence of undetectable or low serum prostate‐specific antigen level , 2007, Cancer.

[28]  A. Jemal,et al.  Cancer Statistics, 2007 , 2007, CA: a cancer journal for clinicians.

[29]  M. Becich,et al.  Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process , 2007, BMC Cancer.

[30]  M. Rogers,et al.  Molecular Cancer Mechanisms of Osteopontin and Cd44 as Metastatic Principles in Prostate Cancer Cells , 2006 .

[31]  G. Jenster,et al.  TMPRSS2:ERG fusion by translocation or interstitial deletion is highly relevant in androgen-dependent prostate cancer, but is bypassed in late-stage androgen receptor-negative prostate cancer. , 2006, Cancer research.

[32]  C. Horak,et al.  c-Met Ectodomain Shedding Rate Correlates with Malignant Potential , 2006, Clinical Cancer Research.

[33]  D. English,et al.  Circulating Insulin-Like Growth Factor-I and Binding Protein-3 and Risk of Prostate Cancer , 2006, Cancer Epidemiology Biomarkers & Prevention.

[34]  H. Fuse,et al.  Serum hepatocyte growth factor activator inhibitor type I (HAI‐I) and type 2 (HAI‐2) in prostate cancer , 2006, The Prostate.

[35]  D. Ribatti,et al.  Serum insulin‐like growth factor is not elevated in patients with early B‐cell chronic lymphocytic leukemia but is still a prognostic factor for disease progression , 2006, European journal of haematology.

[36]  N. Maitland,et al.  Prospective identification of tumorigenic prostate cancer stem cells. , 2005, Cancer research.

[37]  W. Jiang,et al.  Hepatocyte growth factor/scatter factor and prostate cancer: a review. , 2005, Histology and histopathology.

[38]  T. Essam,et al.  Hepatocyte growth factor as a tumor marker in the serum of patients with prostate cancer. , 2005, Journal of the Egyptian National Cancer Institute.

[39]  P. Abbe,et al.  HGF induces fibronectin matrix synthesis in melanoma cells through MAP kinase-dependent signaling pathway and induction of Egr-1 , 2005, Oncogene.

[40]  W. Willett,et al.  Plasma insulin-like growth factor-1 and binding protein-3 and subsequent risk of prostate cancer in the PSA era , 2005, Cancer Causes & Control.

[41]  A. Sundan,et al.  Role of osteopontin in adhesion, migration, cell survival and bone remodeling. , 2004, Experimental oncology.

[42]  P. Stattin,et al.  High levels of circulating insulin-like growth factor-I increase prostate cancer risk: a prospective study in a population-based nonscreened cohort. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  J. Crowley,et al.  Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. , 2004, The New England journal of medicine.

[44]  A. Angelucci,et al.  Osteopontin enhances the cell proliferation induced by the epidermal growth factor in human prostate cancer cells , 2004, The Prostate.

[45]  Matthias Egger,et al.  Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis , 2004, The Lancet.

[46]  Z. Oltvai,et al.  Osteopontin contributes to hepatocyte growth factor-induced tumor growth and metastasis formation. , 2003, Experimental cell research.

[47]  M. Stampfer,et al.  Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. , 2002, Journal of the National Cancer Institute.

[48]  Kenneth M. Yamada,et al.  Fibronectin at a glance , 2002, Journal of Cell Science.

[49]  L. Stitt,et al.  Plasma osteopontin , 2002, Cancer.

[50]  M. Stampfer,et al.  Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. , 2002, Journal of the National Cancer Institute.

[51]  L. Trusolino,et al.  Osteopontin is an autocrine mediator of hepatocyte growth factor-induced invasive growth. , 2001, Cancer research.

[52]  A. Grimberg P53 and IGFBP-3: apoptosis and cancer protection. , 2000, Molecular genetics and metabolism.

[53]  U. Studer,et al.  Osteopontin: possible role in prostate cancer progression. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[54]  A. Renshaw,et al.  Biochemical Outcome after radical prostatectomy, external beam Radiation Therapy, or interstitial Radiation therapy for clinically localized prostate cancer , 1998 .

[55]  J. Kirkpatrick Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. , 1998, Journal of insurance medicine.

[56]  M. Stampfer,et al.  A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer. , 1995, JAMA.

[57]  M. Papa,et al.  Serum insulin-like growth factor-binding protein-2 (IGFBP-2) is increased and IGFBP-3 is decreased in patients with prostate cancer: correlation with serum prostate-specific antigen. , 1993, The Journal of clinical endocrinology and metabolism.

[58]  S. Jalkanen,et al.  Lymphocyte CD44 binds the COOH-terminal heparin-binding domain of fibronectin , 1992, The Journal of cell biology.