Open Access
The TEOGIC study project: a comprehensive characterization of early onset gastrointestinal cancer in the northern area of Spain
(BioMed Central (BMC), 2024) Vera García, Ruth; Castro Unanua, Natalia; Labiano, Ibone; Lecumberri Aznárez, Arturo; Huerta Hernández, Ana Elsa; Arasanz Esteban, Hugo; Caseda Moreno, Irene; Ruiz-Pace, F.; Viaplana, C.; Arrazubi, Virginia; Hernández García, Iker; Mata Velasco, Elena; Gomez, D.; Laguna, S.; Suárez, Javier; Fernández de los Reyes, Irene; Rullán Iriarte, María; Estremera, Fermín; Alonso, V.; Pazo-Cid, Roberto; Gil-Negrete, A.; Lafuente, A.; Martin-Carnicero, A.; Dienstmann, R.; Alsina, María; Ciencias de la Salud; Osasun Zientziak
Background: gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. Methods: patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (¿50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. Discussion: the underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.
Open Access
Next-generation sequencing of bile cell-free DNA for the early detection of patients with malignant biliary strictures
(BMJ Publishing Group, 2021) Arechederra, María; Rullán Iriarte, María; Amat Villegas, Irene; Oyón, Daniel; Zabalza, Lucía; Elizalde, María; Latasa, Maria Ujue; Mercado Gutiérrez, María R.; Ruiz-Clavijo, Daniel; Saldaña, Cristina; Fernández-Urién Sainz, Ignacio; Carrascosa, Juan; Jusué, Vanesa; Guerrero Setas, David; Zazpe, Cruz; González Borja, Iranzu; Sangro, Bruno; Herranz, José M.; Purroy, Ana; Gil, Isabel; Nelson, Leonard J.; Vila, Juan J.; Krawczyk, Marcin; Zieniewicz, Krzysztof; Patkowski, Waldemar; Milkiewicz, Piotr; Cubero, Francisco Javier; Alkorta Aranburu, Gorka; Fernández-Barrena, Maite G.; Urman Fernández, Jesús María; Berasain, Carmen; Ávila, Matías A.; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Objective: despite significant progresses in imaging and pathological evaluation, early differentiation between benign and malignant biliary strictures remains challenging. Endoscopic retrograde cholangiopancreatography (ERCP) is used to investigate biliary strictures, enabling the collection of bile. We tested the diagnostic potential of next-generation sequencing (NGS) mutational analysis of bile cell-free DNA (cfDNA). Design: a prospective cohort of patients with suspicious biliary strictures (n=68) was studied. The performance of initial pathological diagnosis was compared with that of the mutational analysis of bile cfDNA collected at the time of first ERCP using an NGS panel open to clinical laboratory implementation, the Oncomine Pan-Cancer Cell-Free assay. Results: an initial pathological diagnosis classified these strictures as of benign (n=26), indeterminate (n=9) or malignant (n=33) origin. Sensitivity and specificity of this diagnosis were 60% and 100%, respectively, as on follow-up 14 of the 26 and eight of the nine initially benign or indeterminate strictures resulted malignant. Sensitivity and specificity for malignancy of our NGS assay, herein named Bilemut, were 96.4% and 69.2%, respectively. Importantly, one of the four Bilemut false positives developed pancreatic cancer after extended follow-up. Remarkably, the sensitivity for malignancy of Bilemut was 100% in patients with an initial diagnosis of benign or indeterminate strictures. Analysis of 30 paired bile and tissue samples also demonstrated the superior performance of Bilemut. Conclusion: implementation of Bilemut at the initial diagnostic stage for biliary strictures can significantly improve detection of malignancy, reduce delays in the clinical management of patients and assist in selecting patients for targeted therapies.
Open Access
Utilidad del análisis molecular de la bilis en la estenosis biliar maligna
(2024) Rullán Iriarte, María; Urman Fernández, Jesús María; Arechederra, María; Ciencias de la Salud; Osasun Zientziak
La hipótesis de trabajo de la tesis se basa en que la exploración y búsqueda de nuevos biomarcadores en la bilis a través del análisis lipidómico, proteómico y secuenciación del ADN, podrían mejorar el rendimiento diagnóstico de las técnicas actuales anatomopatológicas utilizadas en los pacientes con estenosis biliares. Además de esta mejora, la identificación de los escenarios clínicos en los que utilizarlos y su evaluación económica permitirían seleccionar las técnicas diagnósticas más eficientes para mejorar el manejo de estos pacientes en la práctica clínica habitual (diagnóstico precoz, evitando la repetición de pruebas invasivas e intervenciones innecesarias, identificación de mutaciones accionables que permitan el desarrollo y utilización de tratamientos dirigidos) y así, indirectamente, contribuir a un aumento de la supervivencia de dichos pacientes.

Rullán Iriarte, María

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