Plasma Extracellular Vesicle-Derived TIMP-1 mRNA as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma: A Pilot Study

Abstract

<jats:p>The tumor microenvironment has gained a lot of attention from the scientific community since it has a proven impact in the development of tumor progression and metastasis. Extracellular vesicles (EVs) are now considered one of the key players of tumor microenvironment modulation. Clear cell renal cell carcinoma (ccRCC) is the most lethal urological neoplasia and presents a high metastatic potential, which reinforces the need for the development of more effective predictive biomarkers. Our goal was to evaluate the applicability of EV-derived matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) as prognostic biomarkers for ccRCC. To do so, we studied the plasma EV content of 32 patients with localized ccRCC and 29 patients with metastatic ccRCC. We observed that patients with localized disease and tumors larger than 7 cm presented higher levels of plasma EV-derived TIMP-1 mRNA when compared with patients presenting smaller tumors (p = 0.020). Moreover, patients with metastatic disease presented higher levels of EV-derived TIMP-1 mRNA when compared with patients with localized disease (p = 0.002) and when we stratified those patients in high and low levels of TIMP-1 EV-derived mRNA, the ones presenting higher levels had a lower overall survival (p = 0.030). EV-derived TIMP-1 mRNA may be a good prognostic biomarker candidate for ccRCC.</jats:p>

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

“…Concerning to metastatic ccRCC, an increase of EV-derived miR-301a-3p and a decrease of EV-derived miR-1293 is described [ 45 ]. Apart from miRNAs, EVs-derived tissue inhibitors of metalloproteinases (TIMP-1) mRNA are also included as good prognostic biomarker candidates for ccRCC [ 46 ]. In present work, we highlighted the role of EVs and focused on the strength of mtDNA as a relevant marker for both screening and aggressiveness.…”

Extracellular Matrix-Related Hubs Genes Have Adverse Effects on Gastric Adenocarcinoma Prognosis Based on Bioinformatics Analysis

“…Previous studies indicated that as a part of ECM, TIMP1 could led to accelerated differentiation and hypertrophy of adipocytes, which contributed to the pathogenesis of cancer [ 32 , 33 ]. A recent study showed that high TIMP1 mRNA was associated with a lower OS in clear cell renal cell carcinoma [ 34 ]. This is consistent with our results that a higher TIMP1 level was associated with poor OS in GAC patients.…”

Antitumor Effect of Cabozantinib in Bone Metastatic Models of Renal Cell Carcinoma

“…The evidence showed that the IGFBP2 levels are associated with cancer cell invasion and metastasis [ 23 , 24 , 25 ]; instead, IGFBP7 displays an ambiguous activity as an oncogene or suppressor gene in distinct types of cancers [ 26 ]. A pilot study demonstrated that TIMP-1 is a negative prognostic biomarker in clear cell RCC patients [ 27 ]; conversely, EDA-A2 is known to act as tumor suppressor when it binds its receptor, XEDAR [ 28 , 29 ]. Regarding NRG1, it has been recently demonstrated that it is released by the tumor microenvironment and promotes antiandrogen resistance in prostate cancer [ 30 ].…”