The Pediatric Solid Tumor Translational Research Group of the INCLIVA Health Research Institute participates in the design of a methodology based on the integration of digital and genomic analysis techniques of the elements that are part of the tumor invasion front (interface between tumor and healthy tissue) 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 together with other Spanish research groups of the Low Prevalence Tumor Research Program of the CIBERONC (Centro de Investigación Biomédica en Red de Cáncer) of the Carlos III Health Institute, recently named the Precision Diagnosis and Therapy Group.
Although the uterine cancer It is the most frequent of the female reproductive system, it is of low prevalence in society, which explains a lower knowledge regarding other types of tumors that occur more frequently. Hence the interest of the scientific team in increasing knowledge of these pathologies.
The principal investigators of this work son Rose Walnutcoordinator of the INCLIVA Pediatric Solid Tumor Translational Research Group, and Xavier Matias-Guiu, head of the Pathological Anatomy service at the Bellvitge University Hospital. The development and results of it are summarized in an article recently published in Frontiers in Cell and Developmental Biologywhich is co-authored by Sofia Granados Apariciresearcher 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 already small differences were observed in their antimicrobial response.
According to the authors, the field of precision oncology will benefit from the appearance of this type of tools, since they allow us to determine which of the elements that make up the tumor are key to predict metastasiswhich novel 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 key to predicting metastasis
In this study, developed over two years (from 2020 to the last quarter of 2022), different aspects of the composition of tumor elements in the area of invasion into healthy tissue in adenocarcinoma and leiomyosarcoma biopsy samples, before and after lung metastasis.
First, through analysis of digital image, the behavior of a type of collagen fibers, the reticular fibers, has been studied. The organization of the fibers at the tumor invasion front in other tumors, such as breast cancer, makes it possible to determine whether the tumor behaves more or less aggressively.
Secondly, information has been obtained on the types of immune cells that infiltrate the area of invasion, since these cells have an essential value in the fight against tumor aggressiveness and have allowed the emergence of novel therapies such as immunotherapy.
Finally, the changes at two genomic levels have been 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, researchers have observed a clear association between the arrangement of reticulin fibers, the composition of immune cells, and genomic changes, factors that would indicate that one tumor is more aggressive than the other.
An association has been observed between the arrangement of reticulin fibers, immune cell composition, and genomic changes.
Along with supervision and validation by expert pathologists, the development of these integrative methodologies could be incorporated into routine evaluation to increase accuracy. diagnostic accuracyprognosis and oncological therapy.
Uterine tumors, like other low-prevalence tumors, require collaboration between institutions and hospitals in order to establish cohorts with a sufficient number of patients for research studies.
The study cohort was carried out by contributing samples of patients from the Vall d’Hebron University Hospital and the Bellvitge University Hospital in Barcelona, the Arnau de Vilanova University Hospital in Lleida, the Virgen del Rocío University Hospital in Seville and the Oslo University 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 of CIBERONC. The study, in addition to addressing future clinical alternatives for cancer treatment of aggressive uterine tumors, lays the foundations for close multidisciplinary and cross-sectional collaboration.
In order to develop a more inclusive strategy, an attempt will be made to optimize artificial intelligence systems, biosensors and synthetic 3D models to identify possible therapeutic targets and implement personalized therapeutic regimens.
The study has received funding from the Carlos III Health Institute (ISCIII) and the European Regional Development Fund (FEDER), CIBERONC and Stable Coordinated Groups of the Spanish Association Against Cancer (AECC).
Reference:
Granados-Aparici Sofia, et al. “Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness”. Frontiers in Cell and Developmental Biology (November 2022)
Fuente: Health Research Institute (INCLIVA)
Rights: Creative Commons.