2023-06-21 14:15:48
Researchers have identified new biomarkers for non-small cell lung cancer, the most common lung cancer. These results have been obtained thanks to a new technique that makes it possible to quantitatively analyze patient samples. It is a pioneering methodology that is cheaper and easier to apply than the traditional ones in hospitals and other clinical settings.
The achievement is the work of specialists from the University of Barcelona (UB), the Bioengineering Institute of Catalonia (IBEC) and other entities.
The research team, led by Enrico Almici from IBEC, has verified that certain characteristics of collagen fibers (one of the most abundant components around cancer cells) would be potential indicators to diagnose and predict the evolution of the disease.
“Our new tool can improve the clinical management of surgical patients with this type of cancer, as it can identify those who are most at risk of recurrence and, therefore, can benefit from more exhaustive follow-up and even neoadjuvant therapies.” [complementarias al tratamiento principal]», explains Jordi Alcaraz, professor at the UB Faculty of Medicine and Health Sciences and IBEC researcher, who led the study together with Joan Montero, a researcher from the same faculty and a professor at the Faculty of Physics and director of the IBEC Josep Samitier.
Researchers from the Hospital Clínic in Barcelona, the Parc Taulí University Hospital in Sabadell, the 12 de Octubre University Hospital in Madrid, the Biomedical Research Center for Respiratory Diseases Network (CIBERES) and the Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine Network (CIBERBBN), in Spain.
Lung cancer is the leading cause of cancer-related death in both men and women worldwide, with a five-year survival rate of 18%. Most of these patients are diagnosed with non-small cell lung cancer, which is subdivided into adenocarcinoma, squamous cell carcinoma, and other less common subtypes. There is increasing evidence of the essential role of the collagen fiber-rich environment surrounding cancer cells in the progression of this type of cancer and other solid tumors.
In this tumor setting, a high expression of type I collagen has been associated with a poor prognosis and an increased risk of metastasis. “This evidence has pointed to fibrillar collagens as an important potential source of relevant biomarkers for cancer and has aroused therapeutic interest in understanding their functions in tumor development,” explains Jordi Alcaraz, also a researcher at the Hospital Clínic.
Faced with this challenge, researchers have developed and validated a new digital pathology approach (i.e., the study of disease with digital tools) to quantitatively analyze collagen fibers in tissue samples from patients with non-small cell lung cancer. .
Researchers have developed and validated a new technique to quantitatively analyze collagen fibers in tissue samples from patients with non-small cell lung cancer. (Images: University of Barcelona. CC BY)
A more accessible technique for hospital pathology units
The new methodology is based on digitized images of patient biopsies stained with a dye called picrosirius red (PSR) and viewed with polarized light. The researchers then use the open source software CT-FIRE to automatically segment the individual fibers that appear in the images to quantify relevant features such as length, width, or straightness.
“The standard methodology for analyzing collagen fibers is based on an advanced microscopy technique called second harmonic generation, which requires a double-photon confocal microscope, an expensive type of microscope that requires an expert operator,” he details. “On the contrary,” he continues, “our tool is a cheaper approach that is easier for pathology units to incorporate, as it uses inexpensive staining, PSR, free software such as CT-FIRE, and a microscopy technique accessible by the most hospitals such as polarized light.
Collagen density, an indicator of poor prognosis
The researchers have applied this methodology to analyze 195 samples from patients with adenocarcinoma and squamous cell carcinoma. The results show that the straightness of the fibers would be a potential biomarker to diagnose the disease while the density would be an indicator of poor prognosis. In addition, the prognostic value of collagen density would be “independent of the clinical stage of the tumor, and shows that analyzing the collagen fibers provides additional relevant information”, highlights Jordi Alcaraz.
Abnormal hardening of tissues in patients with adenocarcinoma
The new methodology has also made it possible to compare the characteristics of collagen fibers from patients with non-cancerous tissue samples. In this way, for the first time, they have been able to quantitatively describe the changes that take place in the organization of collagen in non-small cell lung cancer.
The results show that, in the tumor tissue samples, there is an increase in straightness, length and width indicating abnormal hardening of the tissue, especially in patients with adenocarcinoma. According to the researchers, this hardening would be related to different mechanisms to avoid the response of the immune system and, consequently, with the progression of the tumor in this type of cancer. “This opens the door to identifying new therapies directed against abnormal hardening,” concludes the researcher.
Alcaraz, Almici and their colleagues present the technical details of their new methodology and the first results obtained with it, in the academic journal Modern Pathology, under the title “Quantitative Image Analysis of Fibrillar Collagens Reveals Novel Diagnostic and Prognostic Biomarkers and Histotype-dependent Aberrant Mechanobiology in Lung Cancer”. (Source: UB)
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