# Plasma Levels of Aromatase, Cathepsin S and Matrix Metalloproteinase 1 in Renal Cell Carcinomas: Implications for Tumor Progression and Diagnostic Value

## TL;DR

This study explores plasma levels of three proteins in kidney cancer patients, suggesting they could help diagnose and understand tumor progression.

## Contribution

The study introduces a new diagnostic technique using SPRi biosensors to detect ccRCC markers ARO, CTSS, and MMP-1.

## Key findings

- ARO levels were significantly elevated in early-stage ccRCC (T1–T2) and advanced stages (T3–T4).
- CTSS and MMP-1 concentrations increased significantly in advanced-stage tumors (T3–T4).
- A moderate positive correlation was found between the three proteins, suggesting possible interactions in tumor progression.

## Abstract

Kidney cancer (RC) is a prevalent malignant tumor. The main type of kidney cancer is renal cell carcinoma (RCC). Clear cell renal cell carcinoma (ccRCC) is a major histological subtype and is often detected at a locally advanced stage or with distant metastases. In this study, plasma concentrations of aromatase (ARO), cathepsin S (CTSS), and matrix metalloproteinase 1 (MMP-1) were determined in a control group and a group of renal cell carcinoma patients using SPRi biosensors. We examined how the presence of ccRCC affects the concentrations of individual proteins in blood plasma. Levels of the three tested substances increased with tumor stage. CTSS and MMP-1 were significantly elevated in T3–T4 lesions, while aromatase was substantially elevated in T1–T2 and T3–T4.

Background/Objectives: Kidney cancer (RC) is a significant global health burden. Renal cell carcinoma (RCC) is the most common form of kidney cancer. Its predominant histological subtype is clear cell renal cell carcinoma (ccRCC), which is frequently diagnosed at an advanced local stage or with metastases. Detecting cancer at an early stage significantly increases the likelihood of a cure; therefore, research on new markers and a thorough understanding of tumor biology are essential. This study investigated the significance of aromatase (ARO), cathepsin S (CTSS), and matrix metalloproteinase 1 (MMP-1) as potential biomarkers in ccRCC. Methods: ARO, CTSS, and MMP-1 concentrations in plasma were determined using SPRi biosensors. Appropriate antibodies were used as biorecognition molecules in the biosensors. The samples analyzed came from 60 patients with histopathologically confirmed clear cell renal cell carcinoma (ccRCC) and from 26 patients diagnosed with chronic cystitis or benign prostatic hyperplasia (BPH). Results: A statistically significant increase (p < 0.00001) in the concentration of all proteins compared with the control samples was observed at the T3–T4 stage. The ARO concentration was already statistically significantly higher at the T1–T2 stage (p < 0.00001). The ROC curve for aromatase demonstrated high sensitivity and specificity for detecting ccRCC, with a cut-off point of 7.53 ng mL−1. A moderate positive correlation was also found between the concentrations of the three tested substances in renal cancer, which may indicate potential interactions in the tumor’s pathogenesis. Conclusions: SPRI testing has been shown to be an alternative to standard methods for detecting potential ccRCC markers. The biosensors used in the study can simultaneously determine ARO, CTSS, and MMP-1. The results obtained suggest the potential importance of these proteins in the development of ccRCC, and our work proposes a new diagnostic technique that may aid in the diagnosis of ccRCC.