A methodology is designed to detect aggressiveness in uterine tumors and predict metastases

The Translational Research Group on Pediatric Solid Tumors of the Instituto de Investigação em Saúde INCLIVA participates in the design of a methodology based on the integration of digital and genomic analysis techniques of the elements that form part of the tumor invasion front (interface between the tumor tissue and the healthy) to infer aggressiveness in two different types of uterine tumors: adenocarcinomas (tumors that originate in the endometrium) and leiomyosarcomas (tumors that originate in the myometrium).

This project is carried out in conjunction with other Spanish research groups from the Low Prevalence Tumors Research Program of CIBERONC (Centro de Investigación Biomédica en Red de Cáncer) of the Carlos III Health Institute, recently named Grupo de Diagnostico e Terapia de Precision.

Although uterine cancer is the most frequent cancer of the female reproductive system, it has a low prevalence in society, which explains the lower level of knowledge about other types of tumors that occur more frequently. Hence the interest of the scientific team in increasing the knowledge of these pathologies.

The main investigators of this work are Rosa Noguera, coordinator of the Translational Research Group on Pediatric Solid Tumors at INCLIVA, and Xavier Matias-Guiu, head of the Pathological Anatomy service at Bellvitge University Hospital. Its development and results are summarized in a article recently published in Frontiers in Cell and Developmental Biology, co-authored with Sofía Granados Aparici, researcher at INCLIVA.

CIBERONC Scientific Group. / CYBERONC.

The starting point was previous research that used the same tools to assess the differences between these two types of tumors before metastasis. There, small differences in their antimicrobial response have already been observed.

According to the authors, the field of precision oncology will benefit from the emergence of this type of tools, as they make it possible to determine which of the elements that make up the tumor are fundamental to predict metastasis, which new therapies can increase the effectiveness of current treatments and which are more specific and personalized to improve the quality of life of patients.

These types of tools make it possible to determine which of the elements that make up the tumor are fundamental to predict metastasis.

In this study, carried out over two years (from 2020 to the last quarter of 2022), different aspects of the composition of tumor elements in the zone of invasion of healthy tissue were compared in biopsy samples of adenocarcinoma and leiomyosarcoma. , before and after his pulmonary metastasis.

First, through the analysis of digital images, the behavior of a type of collagen fibers, the reticular fibers, was studied. The organization of fibers in front of tumor invasion in other tumors, such as breast, allows determining whether the tumor behaves more or less aggressively.

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Secondly, information was obtained on the types of immune cells that infiltrate the area of ​​invasion, since these cells are of essential value in the fight against tumor aggressiveness and have allowed the emergence of new therapies such as immunotherapy.

Finally, changes at two genomic levels were studied in detail: the epigenomic, which determines how gene activation is facilitated, and the transcriptomic, which shows which genes are active.

Comparing these two types of aggressive tumors of the uterus, the researchers observed a clear association between the arrangement of reticulin fibers, the composition of immune cells and genomic alterations, factors that would indicate that one tumor is more aggressive than the other.

An association was observed between reticulin fiber arrangement, immune cell composition and genomic alterations.

Along with oversight and validation by expert pathologists, the development of these integrative methodologies can be incorporated into routine assessment to increase accuracy at the levels of cancer diagnosis, prognosis and therapy.

Uterine tumors, like other low-prevalence tumors, require collaboration between institutions and hospitals to establish cohorts with a sufficient number of patients for research studies.

The study cohort was carried out by contributing patient samples from Hospital Universitario Vall d’Hebron and Hospital Universitario Bellvitge in Barcelona, ​​​​​​the Hospital Universitario Arnau de Vilanova in Lleida, Hospital Universitario Virgen del Rocío in Seville and the University from Oslo Hospital.

The publication of the article in Frontiers in Cell and Developmental Biology represents the result of collaboration between the different groups of low-prevalence tumors at CIBERONC. The study, in addition to addressing future clinical alternatives for the oncological treatment of aggressive uterine tumors, lays the groundwork for a close multidisciplinary and cross-sectional collaboration.

In order to develop a more integrative strategy, efforts will be made to optimize artificial intelligence systems, biosensors and synthetic 3D models to identify potential therapeutic targets and implement personalized therapeutic regimens.

The study received funding from the Carlos III Health Institute (ISCIII) and the European Regional Development Fund (FEDER), CIBERONC and Stable Coordination Groups of the Spanish Association Against Cancer (AECC).

Reference:

Granados-Aparici Sofia, et al. “Integrating digital pathology with transcriptomics and epigenomics tools to predict metastatic uterine tumor aggressiveness”. Frontiers in Cellular and Developmental Biology (November 2022)

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