The Value of Combined Use of Survivin mRNA and Matrix Metalloproteinase 2 and 9 for Bladder Cancer Detection in Voided Urine

Abstract

Abstract. Objective:In a trial to improve the diagnostic efficacy of conventional urine cytology we determine survivin RNA and matrix metalloproteinase 2 and 9 in urine of bladder cancer cases. Method: Voided urine specimens were collected from patients with histologically confirmed bladder urothelial carcinoma (Group 1; n = 46), urological patients without urothelial carcinoma (Group 2; n = 20), and healthy volunteers (Group 3; n = 20). Urine cytology, survivin RNA was estimated by qualitative nested RT-PCR and MMP-2, MMP-9 activity were detected by gelatin zymography. The expression of survivin RNA and matrix metalloproteinase 2 and 9 in bladder cancer was compared with benign and normal cases. Results: Positivity rates of survivin RNA and MMPs zymography were significantly different among the 3 groups. Urine survivin detection by qualitative nested RT-PCR showed 76.1% sensitivity and 95% specificity. The overall sensitivity, specificity of urinary MMP zymography was 67.3%, 90% respectively. The combined use of urine cytology with urine survivin or MMPs zymography increased sensitivity of urine cytology from 50% to 84.7%. The highest sensitivity (95.6%) was obtained on combining the three markers. Conclusion: Survivin RNA and MMPS zymography can be considered as promising noninvasive markers for bladder cancer early detection. Combined use of the three markers improved the sensitivity for detecting bladder cancer.

Elevated matrix metalloproteinase-9 expression may contribute to the pathogenesis of bladder cancer

“…Additional studies were excluded as they were not case-control or cohort studies (n=19), were irrelevant to the present study (n=4) or possessed incomplete data (n=1). Overall, 23 case-control studies (15,(18)(19)(20)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47), published between 1998 and 2014, were selected for meta-analysis, and consisted of 1,040 bladder cancer patients and 244 healthy control individuals. Among the 23 studies, the study subjects in 3 studies were African, 14 studies enrolled Asian subjects and 6 studies enrolled Caucasian subjects.…”

“…The levels of particular MMPs, including the interstitial collagenase MMP-1, stromelysin-1 MMP-3, gelatinases MMP-2 and MMP-9 and stromelysin-3 MMP-11, are increased in tumor tissues, and promote the invasion of malignant cells, regulate tumor growth and metastasis and are associated with a poor overall survival rate (15). MMP-9 has multiple substrates; however, collagen type IV, the main component of basement membranes, is the most crucial MMP-9 substrate in a tumor microenvironment (16).…”

“…The proteolytic activity of MMP-9 against collagen type IV not only promotes invasion and metastasis, but also releases matrix-bound growth factors and other signaling molecules to promote growth signaling, angiogenesis and an inflammatory response (9,17). Previous studies have revealed that MMP-9 is involved in the pathogenesis of bladder cancer (3,9,15,18); however, alternative studies fail to establish an association between MMP-9 expression and bladder cancer, leading to the conclusion that MMP-9 may not be an effective marker for bladder cancer detection (19,20). Due to the conflicting results of previous studies, the present study investigated the association between MMP-9 and the pathogenesis of bladder cancer using a retrospective meta-analysis.…”

Functional polymorphisms in the matrix metalloproteinase genes and their association with bladder cancer risk and recurrence: A mini‐review

“…MMP belonging to six different groups of MMP were analyzed as tumor biomarkers among breast, pancreatic, lung, colorectal, ovarian, prostate, brain and also bladder cancer patients. Studies intended to find BC biomarkers, as a result of the location of the tumor, were mainly concerned with the differences between urine samples collected from BC patients and healthy controls …”

“…Studies intended to find BC biomarkers, as a result of the location of the tumor, were mainly concerned with the differences between urine samples collected from BC patients and healthy controls. 3,[36][37][38][39] Interaction of MMP with other biomarkers, such as E-cadherin, VEGF in tissue environment and other non-genetic influences, are not yet completely understood, and might also limit its usefulness as a molecular biomarker. In general, molecular biomarkers may represent essential individual cancer susceptibility factors like common SNP, haplotypes, DNA modifications, cytogenetic rearrangements or RNA expression levels.…”