Diagnosis and Prognosis of Prostate Cancer from Circulating Matrix Metalloproteinases and Inhibitors

Abstract

Although prostate cancer (PCa) is the sixth most common type of neoplasm in the world and the second in prevalence among men (10% of all cases), there is shortage of studies focused on primary prevention of the disorder as well as little understanding on its pathophysiology. Currently, the PCa screening tools are the prostate specific antigen (PSA) dosage conjugated to rectal examination and confirmed by prostate biopsy. Despite the name, the PSA presents reduced specificity, being necessary the identification of new biomarkers that allow an earlier and more precise diagnosis and even better prognosis. Several studies have associated matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) to PCa tumorigenesis and metastasis. Most of the studies so far have been carried out by investigating in situ expression of the metalloproteinases, either by transcriptional measures or by immunohistochemistry with biopsy or postoperative tissue. Investigations in human plasma and serum are scarce, and a bibliographical search resulted in 17 studies which are presented and interpreted herein. This narrative review discusses their settings and findings along with aspects related to circulating metalloproteinases as potential biomarkers for diagnosis or prognosis of the prostatic malignancy, expressing the authors' reticent view on their applicability due to the poor quality of evidence available.

Metalloproteinases and Their Inhibitors: Potential for the Development of New Therapeutics

“…The role of specific MMPs and ADAMs in breast [6,72,73], lung [74][75][76][77], prostate [78][79][80], and colorecta [81] cancer progression, invasion, and metastasis has been studied extensively [18,49,82]. MPs carry a multifaceted role in cancer and they can act as a pro-tumorigenic, anti-tumorigenic, or null factor [6], making it difficult to draw a general conclusion on the role of all MPs without considering all the parameters involved in the model of study such as the individual genomic profile, proteomic profile, and experimental conditions.…”

Matrix Metalloproteinase 26 (Mmp-26) Overexpression in Prostatic Adenocarcinoma

“…The prognosis of PC is also associated with age, with older age being the bestestablished risk factor. Studies indicate that both incidence and mortality increase after age 50, with three-quarters of new cases around age 65 2,16 . In this context, we observed that 56% of the patients with PA in our study were between 60 and 69 years old.…”

“…Serum PSA is measured for early detection, staging, and monitoring of the disease. However, it might have low specificity when the values range between 3 and 10 ng/ml, and also showing an increase in benign conditions such as BHP and prostatitis 2,16 . The search for new biomarkers, which combined with PSA can provide greater precision in the diagnosis, has led to several studies on the expression of MMP, both in serum and in tissue samples of PC.…”

“…PC screening tools include serum prostatespecific antigen (PSA) measurement, rectal examination, and biopsy. Despite its name, PSA has low specificity presenting with high levels in benign conditions such as prostatitis and hyperplasia, which results in unnecessary treatment and elevated rates of negative biopsy results 2 . Therefore, research of new biomarkers for early, differential diagnosis and with potential for PC prognostic value has been undertaken.…”

Serum Levels of Matrix Metalloproteinase-1 in Brazilian Patients with Benign Prostatic Hyperplasia or Prostate Cancer

“…Studies indicate that the class of serum proteinases of matrix metalloproteinase (MMP) nature is importantly involved in PCa, with potential utility for the entity's diagnosis [8]. MMPs are zinc-and calcium-dependent endopeptidases that degrade various elements of the extracellular matrix (ECM), especially collagen, elastin, laminin, fibronectin, and proteoglycans, and take part in physiological processes involving tissue remodeling.…”