Abstract
Cathepsin Z (CTSZ) is a cysteine protease responsible for the adhesion and migration of both immune and tumor cells. Due to its dual role, we hypothesized that the site of CTSZ expression could be determinant of the pro- or anti-tumorigenic effects of this enzyme. To test this hypothesis, we analyzed CTSZ expression data in healthy and tumor tissues by bioinformatics and evaluated the expression levels of CTSZ mRNA in the blood cells of prostate cancer (PCa) patients by qRT-PCR compared with healthy subjects, evaluating its diagnostic and prognostic implications for this type of cancer. Immune cells present in the blood of healthy patients overexpress CTSZ. In PCa, we found decreased CTSZ mRNA levels in blood cells, 75% lower than in healthy subjects, that diminished even more during biochemical relapse. CTSZ mRNA in the blood cells had an area under the curve for PCa diagnosis of 0.832, with a 93.3% specificity, and a positive likelihood ratio of 9.4. The site of CTSZ mRNA expression is fundamental to determine its final role as a protective determinant in PCa, such as CTSZ mRNA in the blood cells, or a malignant determinant, such as found for CTSZ expressed in high levels by different types of primary and metastatic tumors. Low CTSZ mRNA expression in the total blood is a possible PCa marker complementary to prostate-specific antigen (PSA) for biopsy decisions, with the potential to eliminate unnecessary biopsies.
Highlights
Prostate cancer (PCa) is the second most incident type of cancer worldwide and the first in the male population, representing the second leading cause of male cancer death in the United States [1]
We have analyzed Cathepsin Z (CTSZ) mRNA expression in terms of different clinical parameters related to the malignancy status, and we found that the group with intermediate/high risk according to the ISUP grade group for the resected tumor (Supplementary Figure S3A) presented a 71% decrease compared to the low-risk group (p=0.050)
For the other parameters analyzed (Supplementary Figure S3C–H) and for the patients submitted to prostatectomy, where we evaluated the expression of CTSZ mRNA in the blood before and six months after the surgical excision of the tumor, no significant difference was found in CTSZ mRNA expression among the groups (Supplementary Figure S4)
Summary
Prostate cancer (PCa) is the second most incident type of cancer worldwide and the first in the male population, representing the second leading cause of male cancer death in the United States [1]. PSA testing improved PCa screening; the specificity, positive likelihood ratio (+LR), and positive predictive value are low [2,3], and approximately one-third of the men with an elevated PSA have PCa detected on biopsy. These data raise concerns since numerous patients are submitted unnecessarily to the risks and discomforts of a prostate biopsy, such as bleeding, infection, and pain. CTSZ is overexpressed in several primary tumor types, such as PCa, colorectal, gastric, liver, melanoma, and pancreatic neuroendocrine tumors [4] In some of these studies, CTSZ was found in tumor-associated macrophages, indicating that this protease plays a role in the antitumor immune response. The CTSZ relationship with integrin receptors is fundamental to allow cell dissemination through the extracellular matrix [7]
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Schedule a callMore From: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
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