Low Specificity of Fibroblast Growth Factor23 In Differentiating Prostate Cancer from Benign Prostate Hyperplasia

  • Kayode S Adedapo
  • Muideen Jimoh
  • A O Takure


Finding a biomarkers that will be more sensitive and specific for the diagnosis of either prostate cancer or BPH as well as differentiating the two clinical conditions beyond the use of total PSA and all the its modifications has been of considerable interest for the Clinicians and other health care providers. This study here posited some further clarifications in this direction. This work attempted to determine the sensitivity/specificity of fibroblast growth factor23 in prostate cancer and benign prostate hyperplasia (BPH) patients at a tertiary centre in Ibadan Nigeria. Anthropometric characteristics, serum fibroblast growth factor 23 (FGF-23) and total prostate specific antigen (tPSA) were determined in 60 patients with histopathological diagnosis of BPH and Pca and thirty age matched control. Informed consent was obtained from all the participants in the study. Serum FGF-23 was determined using enzyme-linked immunosorbent serologic assay (ELISA) and total PSA was determined using enzyme immunoassay (EIA). The statistical analysis was done using SPSS version 20.0 and Receiver operating characteristics (ROC) curve was used to determine the sensitivity and specificity for both FGF-23 and PSA. A p-value < 0.05 was considered significant. The mean FGF-23 was significantly higher in Pca and BPH compared to control. Expectedly, the mean total PSA was also significantly higher in Pca compared to BPH and control. There was a statistically significant AUC for FGF-23(AUC = 0.697, p = 0.009) between PCa patients and controls while PSA was not statistically significant. (AUC = 0.564, p = 0.391). At FGF-23 cut off of 221.45pg/ml, sensitivity and specificity were 66.7 and 83.3 respectively while at PSA cut off of 1.217ng/ml, sensitivity and specificity were 56.7 and 86.7 for diagnosis of prostate cancer respectively. However FGF23 has low specificity in distinguishing patients with prostate cancer from BPH. FGF-23 appears more specific in the diagnosis of both PCa and BPH than total PSA and may be promising in differentiate these two disease entities from individuals without them.

Key words: Benign prostate hyperplasia, fibroblast growth factor 23, prostate cancer, sensitivity, specificity


Adedapo K.S., Arinola O,G., Shittu O.B., Kareem O.I., Okolo C.A., Nwobi L.N., 2012. Diagnostic value of lipids, total antioxidants, and trace metals in benign prostate hyperplasia and prostate cancer. Niger J Clin Pract.; 15:293-7.
Adedapo K.S., Olufemi O., Ogunwale K.T., Shittu O.B., 2014. Could hypertriglyceridaemia be sustainable in discrimination of patients with prostate cancer from benign prostatic hyperplasia? Arch. Appl. Sci. Res.; 6 (4):78-84.
Adedapo K.S., Olusanya T.O., Takure A.O., 2015. Dietary implication of high malondialdehyde, reduced vitamin D and total antioxidant status of prostate cancer subjects in Ibadan. International Journal of Biomedical Research.; 6(09): 661-668
Amayo A., Obara W., 2004.Serum prostate specific antigen levels in men with benign prostatic hyperplasia and cancer of prostate. East Afr Med J.; 81(1):22-6.
Auffenberg G., Helfan B., McVary K., 2009. Established medical therapy for benign prostatic hyperplasia. Urol Clin North Am; 36: 443-459
Berroukche A., Bendahmane-salmi M., Kandouci B., 2012. A case-control study on risk factors of benign prostatic hyperplasia in Algerian aging men. Adult urology; 6(1): 800.
Bosch J.L., Hop W.C., Kirkels W.J., Schröder F.H., 1995. Natural history of benign prostatic hyperplasia: Appropriate case definition and estimation of its prevalence in the community. Urology; 46:34–40.
Cary K.C., Cooperberg M.R., 2013. Biomarkers in prostate cancer surveillance and screening: past, present, and future. Ther Adv Urol.; 5:318–329.
Chan J.M., Stampfer M.J., Ma J., Gann P.H., Gaziano J.M., Giovannucci E.L., 2001 Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study. Am J Clin Nutr.; 74:549–554.]
Delongchamps N.B., Singh A., Haas G.P., 2007. Epidemiology of prostate cancer in Africa: another step in the understanding of the disease? Curr Probl Cancer.; 31(3):226-36.
Edward Giovannucci, Eric B. Rimm, Yan Liu, Michael Leitzmann, Kana Wu, Meir J. Stampfer, Walter C. Willett, 2003. Body Mass Index and Risk of Prostate Cancer in U.S. Health Professionals, JNCI: Journal of the National Cancer Institute.; 95, (16):1240–1244.
Ejike C.E.C.C., L.U.S. Ezeanyika, 2008. Metabolic syndrome in sub-Saharan Africa: Smaller twin of a region's prostatic diseases? Int. Urol. Nephrol.; 40: 909-920.
Ellis W.J., Brawer M.K., 1993. PSA in benign prostatic hyperplasia and prostatic intraepithelial neoplasia. Urol Clin North Am.; 20:621-5.
Ezeanyika L.U.S., C.E.C.C. Ejike, O. Obidoa, S.O. Elom, 2006. Prostate disorders in an apparently normal Nigerian population 1: Prevalence. Biokemistri.; 18: 127-132.
Fong Y.K., Milani S., Djavan B., 2005. Natural history and clinical predictors of clinical progression in benign prostatic hyperplasia. Curr Opin Urol.; 15:35–8.
Gao X., LaValley M.P., Tucker K.L., 2005. Prospective studies of dairy product and calcium intakes and prostate cancer risk: a meta-analysis. Journal of National Cancer Institute. ; 97(23):1768–1777.
Guess H.A., Arrighi H.M., Metter E.J., Fozard J.L., 1990. Cumulative prevalence of prostatism matches the autopsy prevalence of benign prostatic hyperplasia. Prostate.; 17:241–6.
Hak Sun Jang, Jong Sung Kim, Sung Soo Kim, Jin-Gyu Jung, Seok-Joon Yoon, HyunJu Yang, and Hyun Chul Joung, 2017. Relationship between Alcohol Consumption and Prostatic Hyperplasia According to Facial Flushing after Drinking in Korean Men. Korean J Fam Med.; 38(2): 93–98.
Horwich A., ParkerC., Bangma C., Kataja V., 2010. On behalf of the ESMO Guidelines Working GroupAnnals of Oncology.; 21(5):v129–v133 https://doi.org/10.1093/annonc/mdq174.
Howard D. Sesso, Ralph S. Paffenbarger, Jr. , I-Min Lee, 2001. Alcohol consumption and risk of prostate cancer: The Harvard Alumni Health Study. International Journal of Epidemiology.; 30(4): 749–755.
Itoh N., Ornitz D.M., 2004. Evolution of the Fgf and Fgfr gene families. Trends Genet.; 20: 563 –569.
Jacobsen S.J., Jacobson D.J., Girman C.J., Roberts R.O., Rhodes T., Guess H.A., 1997. Natural history of prostatism: Risk factors for acute urinary retention. J Urol.; 158:481–7.
Kalcher K., Kern W., Pietsch R., 1993. Cadmium and lead in the smoke of a filter cigarette. Sci. Total Environ.; 128:21-35.
Kim H.J., Kim K.H., Lee J., Oh J.J., Cheong H.S., Wong E.L., Yang BS, Byun S.S., Myung S.C., 2014. Single nucleotide polymorphisms in fibroblast growth factor 23 gene, FGF23, are associated with prostate cancer risk. BJU International.; 114:303–310.
Kocełak P.,Olszanecka-Glinianowicz M.,Chudek J., 2012. Fibroblast growth factor 23--structure, function and role in kidney diseases. Adv Clin Exp Med.; 21(3):391-401.
Kok E.T., Schouten B.W., Bohnen A.M., Groeneveld F.P., Thomas S., Bosch J.L., 2009. Risk factors for lower urinary tract symptoms suggestive of benign prostatic hyperplasia in a community based population of healthy aging men: The Krimpen study. J Urol.; 181:710–6.
Kramer G., D. Mitteregger, M. Marberger, 2007. Is Benign Prostatic Hyperplasia (BPH) animmune inflammatory disease? Eur. Urol.; 51: 1202-1216.
Lee C., Kozlowski J., Grayhack J., 1997. Intrinsic and extrinsic factors controlling benign prostatic growth. Prostate.; 31: 131.
Mak M.P., da Costa e Silva V.T., Martin R.M., Lerario A.M., Yu L., Hoff P.M., de Castro G., Jr 2012. Advanced prostate cancer as a cause of oncogenic osteomalacia: an underdiagnosed condition. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer.; 20:2195–2197.
McLaren I.D., Jerde T.J., Bushman W., 2011. Role of interleukins, IGF and stem cells in BPH differentiation.; 82: 237-243.
McVary K.T., Roehrborn C.G., Avins A.L., Barry M.J., Bruskewitz R.C., Donnell R.F., 2011. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol.; 185:1793–803.
Nandeesha H., 2008. Benign prostatic hyperplasia: dietary and metabolic risk factors. Int Urol Nephrol.; 40: 649–656.
Odedina F.T., Ogunbiyi J.O., Ukoli F.A., 2006. Roots of prostate cancer in African-American men. J Natl Med Assoc.; 98(4):539-43.
Parsons J.K. 2007. Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms: new approaches to old problems. J Urol.; 178: 395–401.
Parsons J.K., A.V. Sarma, K. McVary, J.T. Wei, 2013. Obesity and benign prostatic hyperplasia: Clinical connections, emerging etiological paradigms and future directions. J. Urol.; 189: S102-S106.
Parsons J.K., Sarma A.V., McVary K., Wei J.T. 2009. Obesity and benign prostatic hyperplasia: clinical connections, emerging etiological paradigms and future directions. J Urol.; 182 (6): S27–S31.
Patel N.D., J.K. Parsons, 2014. Epidemiology and etiology of benign prostatic hyperplasia and bladder outlet obstruction. Ind. J. Urol.; 30: 170-176.
Philip H., Amman B., Deborah E., Ben C., Aphrodite I., Mary W., 2009. A systematic review of the diagnostic accuracy of prostate specific antigen. BMC Urol.; 9: 14.
Platz E.A., Rimm E.B., Kawachi I., Colditz G.A., Stampfer M.J., Willett W.C., Giovannucci E., 1999. Alcohol consumption, cigarette smoking, and risk of benign prostatic hyperplasia. Am J Epidemiol.; 149:106–15.
Quarles L.D., 2012. Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nat Rev Endocrinol.; 8(5): 276–286.
Robert G., A. Descazeaud, Y. Allory, F. Vacherot, A. de la Taille, 2009. Should we investigate prostatic inflammation for the management of benign prostatic hyperplasia? Eur. Urol. Suppl.; 8: 879-886.
Roberts R.O., Jacobsen S.J., Rhodes T., Guess H.A., Girman C.J., Panser L.A., Chute C.G., Oesterling J.E., Lieber M.M., 1994. Cigarette smoking and prostatism: a biphasic association? Urology.; 43:797–801.
Roehrborn C.G., McConnell J., Bonilla J., 2000. Serum prostate specific antigen is a strong predictor of future prostate growth in men with benign prostatic hyperplasia. PROSCAR long-term efficacy and safety study. J Urol.; 163:13–20.
Romero O.J., Garcia G.B., Campos J.F., Touijer K.A., 2014. Prostate cancer biomarkers: an update. Urol Oncol.; 32:252–260.
Saldivar L., Luna M., Reyes E., Soto R., Fortoul T. I., 1991. Cadmium determination in Mexican-produced tobacco. Environ Res.; 55:91-96.
Sinha R., Park Y., Graubard B.I., Leitzmann M.F., Hollenbeck A., Schatzkin A., 2009. Meat and meat-related compounds and risk of prostate cancer in a large prospective cohort study in the United States. Am J Epidemiol.; 170:1165–77.
Stamey T.A., Yang N., Hay A.R., 1987. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med.; 317 (15):909-16.
Stroup S.P., Palazzi-Churas K., Kopp R.P., Parsons J.K., 2012. Trends in adverse events of benign prostatic hyperplasia (BPH) in the USA, 1998 to 2008. BJU Int.; 109:84–7.
Tantiwong A., Nuanyong C., Vanprapar N., Swasdipala P., Chittapraphai S. 2002. Benign prostatic hyperplasia in elderly Thai men in an urban community: The prevalence, natural history and health related behavior. J Med Assoc Thai.; 85:356–60.
Taylor B.C., Wilt T.J., Fink H.A., Lambert L.C., Marshall L.M., Hoffman A.R., 2006. Prevalence, severity, and health correlates of lower urinary tract symptoms among older men: The MrOS study. Urology.; 68:804–9.
Wei J.T., Calhoun E., Jacobsen S.J., 2005. Urologic diseases in America project: Benign prostatic hyperplasia. J Urol.; 173:1256–61.
Yamashita T., Yoshioka M., Itoh N., 2000. Identification of a novel fibroblast growth factor, Biochem Biophys Res Commun.; 277: 494 –498.
Yeargan R., Maiti I. B., Nielsen M. T., Hunt A. G., Wagner G. J., 1992. Tissue partitioning of cadmium in transgenic tobacco seedlings and field grown plants expressing the mouse metallothionein I gene.Transgenic Res.; 1:261-267.
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