Abstract

Renal cell carcinoma (RCC) is the most prevalent and lethal malignancy of the kidney. Despite all the efforts made, no tissue biomarker is currently used in the clinical management of patients with kidney cancer. A search for possible biomarkers in urine for clear cell renal cell carcinoma (ccRCC) has been conducted. Non-targeted metabolomic analyses were performed on paired samples of surgically removed renal cancer and normal tissue, as well as on urine samples. Extracts were analyzed by liquid chromatography/high-resolution mass spectrometry (LC-HRMS). Hydroxybutyrylcarnitine, decanoylcarnitine, propanoylcarnitine, carnitine, dodecanoylcarnitine, and norepinephrine sulfate were found in much higher concentrations in both cancer tissues (compared with the paired normal tissue) and in urine of cancer patients (compared with control urine). In contrast, riboflavin and acetylaspartylglutamate (NAAG) were present at significantly higher concentrations both in normal kidney tissue as well as in urine samples of healthy persons. This preliminary study resulted in the identification of several compounds that may be considered potential clear cell renal carcinoma biomarkers.Graphical abstractPLS-DA plot based on LC-MS data for normal and cancer human tissue samples. The aim of this work was the identification of up- and downregulated compounds that could potentially serve as renal cancer biomarkers.

Highlights

  • Biomarkers provide a powerful approach to understanding diseases with applications in epidemiology, clinical trials, screening, diagnosis, and prognosis

  • Each feature is associated with an exact mass, a retention time, and average abundancies in cancer and normal tissue, as well as with urine samples from patients with and without renal cancers

  • Liquid chromatography/high-resolution mass spectrometry analysis of extracts from cancer and healthy tissue regions allowed the identification of up- and downregulated compounds that could potentially serve as renal cancer biomarkers, clear cell renal cell carcinoma (ccRCC)

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Summary

Introduction

Biomarkers provide a powerful approach to understanding diseases with applications in epidemiology, clinical trials, screening, diagnosis, and prognosis. Efficient biomarkers can reflect the entire spectrum of disease from the earliest manifestation to the terminal stage. The development of cancer therapies is increasingly dependent on the understanding of tumor biology, and biomarkers are becoming essential tools in the field of medicine. Renal cell carcinoma (RCC) is the most prevalent and lethal malignancy of the kidney, accounting for nearly 90% of all renal tumors and representing 2–3% of all adult malignant tumors [1, 2]. RCC is among the ten most common cancers worldwide and is the second most lethal urinary cancer after bladder. According to statistics published by GLOBOCAN in 2012, there were approximately 337,800 new cases of renal cancer and 143,400 kidney cancer-related deaths worldwide [3]

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