Prostatic biopsy, though the gold standard investigation for prostate malignancy, often leads to unnecessary investigation with several complications. Our aim was to find out the cut off values, sensitivity, specificity and predictive values of urinary matrix metalloproteinases, their tissue inhibitors and free PSA to ascertain their suggestive role as noninvasive diagnostic tool for prostate cancer.  Early morning urine samples of 40 clinically suggestive patients were collected and ELISA was done for MMP 7, 13, TIMP 1, 2 and free PSA followed by TRUS guided prostate biopsy. Values of MMP 7 and MMP 13 were found to have significant difference in levels between benign and malignant conditions. The cut off values in urine were obtained as free PSA>2.5mg/l, MMP 7>1ng/ml, MMP 13->75ng/ml, TIMP 1>4000pg/ml and TIMP 2>100pg/ml. MMP 13 and MMP 7 showed high sensitivity, specificity and predictive values while the tissue inhibitors and free PSA showed moderate to low sensitivity and specificity. MMP 13 having the most significant beta coefficient (0.263) was found to be the most significant parameter studied for diagnosing prostate carcinoma. Thus in the present study among different urinary parameters we found that MMP 13 is the most diagnostic tool for detecting prostate cancer followed by MMP 7 with doubtful roles of TIMP 1,TIMP 2 and free PSA.

Keywords: mmp7, mmp 13, timp 1, timp 2, free psa.

1. Ferlay J, Soerjomataram I, Dikshit R, et al, Cancer incidence and mortality worldwide sources, methods and major patterns in GLOBOCAN 2012, Int J Cancer 2015; 136(5):E359-86.
2. Barry MJ. Clinical practice .Prostate-specific antigen testing for early diagnosis of prostate cancer. N  Engl J Med. 2001 May 3;344(18):1373-7.
3. Force USPST. Talking with your patients about screening for Prostate Cancer PDF Retrieved 2012-07-02. May 22,2012.
4. Morgia G, Falsaperia M, Malaponte G, Madonia M, Indelicato M, TraveliS,et al. Matrix metalloproteinases as diagnostic ( MMP -13) and prognostic (MMP-2,MMP-9) markers of prostate cancer.Urol Res 2005 Feb ;33(1): 44-50.
5. Di Carlo A, Mariano A, TetraccianoD,et al. Matrix metalloproteinase-2 and -9 in the urine of prostate cancer patients. Oncol Rep2010;24(1):3-8.

6. Brehmer B, Biesterfeld S, Jakse G. Expression of matrix metalloproteinases (MMP-2 and MMP- 9) and their inhibitors (TIMP-1 and TIMP-2) in prostate cancer tissue. Prostate cancer Prostatic Dis 2003; 6(3):217-22.
7. Zhong WD, Han ZD, He HC, et al. CD147,MMP-1,MMP-2 and MMP-9 protein expression as significant prognostic factors in human prostate cancer .Oncology 2008;75 (3-4):230-6.

1. Gong Y, Chippada-Venkata UD, Oh WK. Roles of matrix metalloproteinases and their natural inhibitors in prostate cancer progression. Cancers (Basal). (Original Article).2014;27(6)(3):1298l
2. World Medical Association Inc. Declaration of Helsinki. Ethical principles for medical reseach involving human subjects..J Indian Med Assoc 2009;107(6):403

10. Miyata Y, Iwata T, Ohba K, Kanda S, Nishikido M, Kanetake H. Expression of matrix metalloproteinase-7 on cancer cells and tissue endothelial cells in renal cell carcinoma: prognostic implications and clinical significance for invasion and metastasis. Clin Cancer Res. 2006 Dec 1; 12(23):6998-7003.
11. Jones LE, Humphreys MJ, Campbell F, Neoptolemos JP, Boyd MT. Compre-hensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer:increased expression of matrix metalloproteinase-7 predicts poor survival .Clin Cancer Res.2004 Apr15;10(8):2832-45.
12. Szarvas T, Becker M, Vom Dorp F, Meschede J, Scherag A, Bankfalvi A, etal. Elevated serum matrix metalloproteinase 7 levels predict poor prognosis after radicalprostatectomy. IntJ Cancer.2011 Mar 15;128(6):1486-92.
13. Morgia G, Falsaperla M, Malaponte G, Madonia M,Indelicato M,TravaliS,et al. Matrix metalloproteinases as diagnostic (MMP-13) and prognostic (MMP-22, MMP-9) markers of prostate cancer. Urol Res.2005 Feb;33(1):44-50
14. Deng X, He G, Levine A, Cao Y,Mullins C. Adenovirus mediated expression of TIMP-1 and TIMP-2 in bone inhibits osteolytic degradation by human prostate cancer. Int J Cancer.2008 Jan 1;122(1):209-18.
15. Lee SJ, Yoo HJ, BaeYS,Kim HJ, Lee ST.TIMP-1 inhibits apoptosis in breast carcinoma cells via a pathway involving pertussis toxin-sensitive G protein and c-Src. Biochem Biophys Res Commun.2003 Dec 26;312(40:1196-201.
16. Chen Y, Wei X, Guo C, Jin H, Han Z, Han Y, et al. Runx3 supresses gastric cancer metastasis through inactivation of MMP 9 BY UPREGULATION OF timp-1. Int J Cancer.2011 Oct 1;129(7):1586-98.

1. Boulday G, Fitau J, Coupel S, Soulillou JP, Charreau B. Exogenous tissue inhibitor of metalloproteinase-1 promotes endothelial cell survival through activation of the phosphatidylinositol 3-kinase/Akt pathway. Ann N Y Acad Sci.2004 Dec; 1030:28-536.
2. Guedez L, Martinez A, Zhao S, Vivero A, Pittaluga S, Stetler-Stevenson M, et al. Tissue inhibitor of metalloproteinase 1 ( TIMP-1) promotes plasmablastic differentiation of a Burkitt lymphoma cell line : implications in the pathogenesis of plasmacytic/plasmabistic tumors. Blood.2005 Feb 15;105(4):1660-8.
3. Hayakawa T,Yamashita K, Tanzawa K, Uchijima E, Iwata K. Growth-promoting activity of tissue inhibitor of metalloproteinases-1(TIMP-1) for a wide range of cells. A possible new growth factor in serum .FEBS Lett. 1992 Feb 17;298(1):29-32.
4. Bigelow RL, Williams BJ, Caroll JL, Daves LK, Cardelli JA. TIMP-1 over expression promotes tumorigenesis of MDA-MB-231 breast cancer cells and alters expression of a subset of cancer promoting genes in vivo distinct from those observed in vitro. Breast Cancer Res Treat. 2009 Sep;117(1):31-44.
5. Xia Y, Yeddula N, Leblanc M, KeE , Zhang Y, Oldfield E, et al. Reduced cell proliferation by IKK2 depletion in a mouse lung-cancer model. Nat Cell Biol. 2015 Apr;17(4):532.
6. Xia Y, Yeddula N, Leblanc M, Ke E, Zhang Y, Oldfield E, et al Reduced cell proliferationby IKK2 depletion in a mouselung cancer model. Nat Cell Biol.2012 Mar;14(3);257-65.
7. Zeng ZS, Cohen AM, Zhang ZF, Stetler-Stevenson W,Guillen JG. Elevated tissue inhibitor of metalloproteinase 1 RNA in colorectal cancer stroma correlates with lymph node and distant metastasis. Clin Cancer Res. 1995 Aug;1(8):899-906.
8. Nilson O, Peter A, Anderson I, Nilsson K, Grunstrom B, Karlsson B,. Antigenic determinants of prostate-specific antigen and the human kallikrien gene family: a new era. Urology. 1995 May; 45(5):729-44.

Dr Jayanta Kumar Rout

Assistant Professor, Dept. of Biochemistry, 4th Floor, Academic Building,

R G Kar Medical College, 1, Kshudiram Bose Sarani, Kolkata: 700004 West Bengal, India

Email: This email address is being protected from spambots. You need JavaScript enabled to view it., Contact no:+919434978759