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Dr Kayode S AdedapoPrincipal Investigator
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• Currently, prostate-specific antigen (PSA) is the most commonly used serum biomarker for the screening and diagnosis of prostate cancer
• However, PSA is not a cancer-specific marker, it has poor specificity.
• Consequently, there is great need for additional serum biomakers to supplement or replace PSA for the detection of prostate cancer in patients.
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One of such prostate cancer biomarker is α-methylacyl-CoA racemase (AMACR),
an enzyme that catalyses the racemization of R-stereoisomers of branched-chain fatty acids to S-stereoisomers
plays an important role in peroxisomal β-oxidation of branched-chain fatty acids (Ferdinandusse et al, 2000; Kotti et al, Schmitz et al, 1995).[1-3]
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AMACR has been shown to be elevated in prostate cancer by several recent studies.
Chandan et al, 2004[4] have presented evidence that AMACR activity is consistently elevated in prostate cancer tissue specimens relative to benign epithelia.
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• Alpha-methylacyl-CoA racemase (AMACR) has been shown, by recent studies, to be over expressed in prostate cancer epithelia;
• Studies on prostate tissue specimens have demonstrated that AMACR protein is a highly specific and sensitive marker for prostate cancer.
• It is therefore necessary to investigate further, especially in this part of the world, the expression of AMACR in prostate cancer patients as a prospective molecular biomarker for the disease.
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• Prostate cancer is becoming an increasingly important public health problem among adult men in most western communities.
• Nigeria, which was formerly regarded as a low-incidence area is no longer left out
• (Ukoli et al, 2003; Ogunbiyi and Shittu, 1999; Parkin et al, 1997; Osegbe, 1997) Asserted a steep rise in the occurrence of the disease.
• Many notable Nigerians have lost their lives to this dreaded disease.
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To test whether α-methylacyl CoA racemase (AMACR) is a sensitive and specific maker for prostate cancer.
To test whether high level of IGF-1 is a risk factor to prostate cancer.
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• To determine the expression level of AMACR by immunohistochemical techniques in Nigerian patients with prostate cancer and benign prostatic hyperplasia as controls.
• To determine immune response to AMACR in plasma of the patients and controls using ELISA method.
• To determine the sensitivity and specificity of AMACR immunodetection of prostate adenocarcinomas in comparison to total prostate-specific antigen.
• To determine the IGF-1 and IGFBP-3 in plasma of the patient and controls using ELISA method.
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Alpha-methylacyl CoA racemase (AMACR) is a biochemical marker of prostate cancer with high sensitivity and specificity.
High insulin-like growth factor-1 ( IGF-1) level is a risk factor for prostate cancer.
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• Is there any significant difference in the expression of AMACR in prostate cancer tissue and BPH tissue?
• Is there any significant difference in the plasma levels of immune response to AMACR in prostate cancer samples and that of BPH?
• Is the IGF-1 levels in patients with prostate cancer samples significantly different from that of BPH?
• What is the type of association between IGF-1 and IGFBP-3?
• Any other correlation between IGF-1 and other selected variable risk factors?
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10 mls blood from histology proven subjects with prostate cancer and Benign prostate hyperplasia:
For Humoral respose to AMACR IGF-1 IGFBP-3 Immnuhistochemistry for AMACR
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Categories of Assay Kit
AMOUNT
IGF – 1 ELISA Kit IGF – 3 ELISA Kit Immunohistochemistr
y Kit) Kit For AMACR
Autoantibodies Needle and Syringe Sample Bottles Total
180,000 190,000 270,000
230,000
6000 6000 882,000
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Professor Olayiwola ShittuDepartment of Surgery, COM., UI.
Dr. C. A. OkoloDepartment of Pathology, COM., UI
PhD Research student, Mr. Clement Famurewa
Dr Adura AdedapoDepartment of Pharmacology and Therapeutics, COM, UI.
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Ferdinandusse S, Denis S, Lodewijk I, Dacremont G, Waterham HR, Wanders RJ. Subcellcular localization and physiological role of alpha-methylacyl – CoA racemase. J. Lipid Res. 2000; 41: 1890-6.
Kotti TJ, Savolainen K, Helander HM, Yagi A, Novikov DK, Kalkkinen N, et al. In mouse alpha – methylacyl – CoA racemase, the gene product is simultaneously located in mitochondria and peroxisomes. J. Biol Chem 2000; 275:20887 – 95.
Ukoli F, Osime V, Akereyeni F, Okunzuwa O, Kittles R, Adanis-Campebell L. Prevalences of elevated serum prostate specific antigen in rural Nigeria. Int. J. Urology 2003; 10(6): 315 – 322.
Ogunbiyi JO, Shittu OB. Increased incidence of prostate cancer in Nigerians. J. Natl. Med. Assoc. 1999; 91:159-164.
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Parkin DM, Whelan SL, Ferlay J, et al. Cancer Incidence of five continents vol. 7, Lyons, France: IARC; 1997.
Osegbe DN. Prostate Cancer in Nigerians:
Facts and Non-facts. J. Urol. 1997; 157 : 1340 – 1343.