A Novel Panel of 80 RNA Biomarkers with Differential Expression in Multiple Human Solid Tumors against Healthy Blood Samples.

Delmonico Delmonico,Qureshi Qureshi,Obenauer Obenauer,Fournier Fournier,Alves Alves,Martin Martin,Costa Costa

doi:10.3390/ijms20194894

Abstract

The aim of this study was to identify genes with higher expression in solid tumor cells by comparing human tumor biopsies with healthy blood samples using both in silico statistical analysis and experimental validations. This approach resulted in a novel panel of 80 RNA biomarkers with high discrimination power to detect circulating tumor cells in blood samples. To identify the 80 RNA biomarkers, Affymetrix HG-U133 plus 2.0 microarrays datasets were used to compare breast tumor tissue biopsies and breast cancer cell lines with blood samples from patients with conditions other than cancer. A total of 859 samples were analyzed at the discovery stage, consisting of 417 mammary tumors, 41 breast lines, and 401 control samples. To confirm this discovery, external datasets of eight types of tumors were used, and experimental validation studies (NanoString n-counter gene expression assay) were performed, totaling 5028 samples analyzed. In these analyses, the 80 biomarkers showed higher expression in all solid tumors analyzed relative to healthy blood samples. Experimental validation studies using NanoString assay confirmed the results were not dependent of the gene expression platform. A panel of 80 RNA biomarkers was described here, with the potential to detect solid tumor cells present in the blood of multiple tumor types.

Highlights

Cancer mortality continues to be a major healthcare problem, despite of decades of advances in the area of oncology [1]
The challenge in finding specific biomarkers for detecting circulating tumor cells (CTCs) in the bloodstream is in the ability to eliminate signs of gene expression from blood cells, such as leukocytes and erythrocytes, in addition to non-tumoral epithelial cells
We analyzed multiple studies using genome-wide gene expression microarrays (Affymetrix HG-U133A) of breast tumor cells and compared them with blood samples from individuals with conditions other than cancer to find high expressing genes in tumor samples that are expressed in blood at the background level

Summary

Introduction

Cancer mortality continues to be a major healthcare problem, despite of decades of advances in the area of oncology [1]. The reason for this problem is that before many cancers are discovered, they have already progressed and become drug-resistant or have metastasized [2]. The recent introduction of liquid biopsies using biomarkers found in blood has offered a valuable opportunity for development of clinical oncology tests to provide better diagnosis, surveillance, and prediction of outcomes, thereby reducing cancer mortality [3]. Biomarkers in blood have the potential to detect a wide variety of primary tumors and metastases located throughout the body. A number of technologies have been developed for the isolation and detection of these components, only a few of these have been successfully translated to the clinic because of shortcomings in sensitivity and specificity [4,5,6]

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