On the trail of new biomarkers to detect glioblastoma and colorectal cancer

A new study by the IIS Aragón and the Aragón Engineering Research Institute, published by the Scientific Society of Biofabrication, recreates tumors in 3D models and analytical chemistry techniques to open new, less invasive diagnostic pathways that improve the prognosis of patients.

Early detection of tumors remains a major challenge for science, so advances in early detection for better diagnosis are a key aspect. Two research groups from the I3A (Institute for Engineering Research of Aragon), at the University of Zaragoza, and the IIS Aragón (Aragon Health Research Institute) are working on this. Thanks to this collaboration, they have developed An organ-on-chip device to recreate tumors in vitro, and through gas chromatography analytical techniques – mass spectrometry (GC-MS), have identified new biomarkers volatiles that can help in the detection of one of the most complex brain tumors, glioblastoma, and also in colorectal cancer.

New biomarkers volatiles that can help in the detection of one of the most complex brain tumors, glioblastoma, and also in colorectal cancer.

The importance of this research is shown in the case of the brain tumors such as glioblastoma, where 25% of patient tissue biopsies are inconclusive, in addition to the difficulty of accessing some tumors and the risk of extraction. The aim is to improve diagnosis and, therefore, the prognosis of patients.

Each tumor with its fingerprint of compounds

In the study, published in the International Society for Biofabrication's scientific journal “Biofabrication,” the research team at the Tissue Microenvironment Laboratory (TME Lab) used a microfluidic device to recreate the ischemic environment within solid tumors and thereby isolate the compounds secreted by the tumors. Subsequently, with the samples, the University Analytical Research Group (GUIA) analyzed the composition of volatile organic compounds. They carried out a qualitative analysis in which up to 32 compounds were detected. The compounds were grouped by chemical families (alkanes, alcohols, phenols, nitrogen compounds, aldehydes and esters) and the volatile profiles between different samples were compared, finding significant differences.

The results showed that Each tumor type secreted a unique fingerprint of compounds, and that this mark is characteristic of the developed tumor.

Metabolic changes in a complex microenvironment

As explained by researchers Clara Bayona (TME Lab) and Jesús Salafranca (GUIA), the progression of the tumor towards a complex microenvironment produces different metabolic changes depending on the type of tumor. Their model has allowed them to generate this tumor microenvironment in vitro for both glioblastoma and colorectal cancer and to detect significant differences in the compounds found.

The TME Lab (Tissue Microenvironment) research group has been responsible for creating these organ-on-chip devices, complex 3D models that recreate a tumor in different microenvironments. They have applied the analytical techniques provided by the University Analytical Research Group (GUIA), which has allowed them to see which cells are specific to a tumor in a patient.

What are volatile organic compounds?

In liquid biopsies, volatile organic compounds (VOCs) have been the focus of scientific attention in recent years as potential biomarkers. These are molecules generated by cellular metabolism that are released into the blood and can be detected directly in the circulation or through the lungs, urine or skin.

However, distinguishing tumor-specific VOCs is difficult due to the presence of gases from non-tumor tissues and environmental factors.

It is essential to develop preclinical models that accurately mimic the complex tumor microenvironment to induce cellular metabolic changes and the secretion of these tumor-associated compounds.

Reference: Clara Bayona et al 2024 Biofabrication. https://doi.org/10.1088/1758-5090/ad5764

Main photo: Jesus Salafranca (GUIDE) y Clara Bayona (TME_Lab) in one of the I3A laboratories.