Articles publicats (Ciències Mèdiques Bàsiques)
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- ItemEmbargoComparison of the differential effect of participation in breast cancer screening program versus opportunistic screening or symptomatic detection on tumour characteristics(Wolters Kluwer Health, 2025-06-01) Laza-Vásquez, Celmira; Rué i Monné, Montserrat; Fougo, José Luís; Peleteiro, BárbaraObjectives: The success of a breast cancer screening program is highly dependent on adherence. We aimed to compare the differential effect of participation in breast cancer screening program versus opportunistic screening or symptomatic detection on tumour characteristics. Methods: We included women referred to our Breast Centre in 2015-2021: 321 from the breast cancer screening group (group 1) and 422 through opportunistic screening or due to symptomatic detection (group 2). We compared data on sociodemographics, breast cancer detection, clinical features and tumour characteristics. Results: A total of 10.6% of women in group 1 had breast symptoms and 63.8% had breast signs, with group 2 presenting higher proportions (57.6 and 77.8%, respectively, P < 0.001). The median tumour size in group 1 was smaller compared with group 2 (14 vs 17 mm, P < 0.001). A total of 8.7% of women in group 1 had nodal involvement whereas in group 2 the proportion corresponded to 19.0% ( P < 0.001). No women in group 1 were diagnosed with metastasis, while metastases were found in 2.4% of those from group 2 ( P = 0.005). There were no significant differences in molecular subtype of invasive tumours between the two groups. Conclusion: The tumour characteristics of women who participated in the breast cancer screening program showed in almost all characteristics more favourable results in comparison with the group who underwent opportunistic screening or sought care due to symptoms. The lower clinical stage observed in those referred from the organised program reaffirms that it is an effective measure for early detection, diagnosis, and treatment.
- ItemOpen AccessSingle-cell RNA sequencing-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma(Elsevier, 2025) Cappuyns, Sarah; Piqué-Gili, Marta; Esteban-Fabró, Roger; Philips, Gino; Balaseviciute, Ugne; Pinyol, Roser; Gris-Oliver, Albert; Vandecaveye, Vincent; Abril-Fornaguera, Jordi; Montironi, Carla; Bassaganyas, Laia; Peix, Judit; Zeitlhoefle, Marcus; Mesropian, Agavni; Huguet-Pradell, Júlia; Haber, Philipp K.; Figueiredo, Igor; Ioannou, Giorgio; Gonzalez-Kozlova, Edgar; D’Alessio, Antonio; Mohr, Raphae; Meyer, Tim; Lachenmayer, Anja; Marquardt, Jens U.; Reeves, Helen L.; Edeline, Julien; Finkelmeier, Fabian; Trojan, Jörg; Galle, Peter R.; Foerster, Friedrich; Mínguez, Beatriz; Montal Roura, Robert; Gnjatic, Sacha; Pinato, David J.; Heikenwalder, Mathias; Verslype, Chris; Van Cutsem, Eric; Lambrechts, Diether; Villanueva, Augusto; Dekervel, Jeroen; Llovet, Josep M.Background & Aims The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit vs. resistance to atezo+bev. Methods We harnessed the power of single-cell RNA sequencing in advanced HCC to derive gene expression signatures recapitulating 21 cell phenotypes. These signatures were applied to 422 RNA-sequencing samples of patients with advanced HCC treated with atezo+bev (n = 317) vs. atezolizumab (n = 47) or sorafenib (n = 58) as comparators. Results We unveiled two distinct patterns of response to atezo+bev. First, an immune-mediated response characterised by the combined presence of CD8+ T effector cells and pro-inflammatory CXCL10+ macrophages, representing an immune-rich microenvironment. Second, a non-immune, angiogenesis-related response distinguishable by a reduced expression of the VEGF co-receptor neuropilin-1 (NRP1), a biomarker that specifically predicts improved OS upon atezo+bev vs. sorafenib (p = 0.039). Primary resistance was associated with an enrichment of immunosuppressive myeloid populations, namely CD14+ monocytes and TREM2+ macrophages, and Notch pathway activation. Based on these mechanistic insights we define "Immune-competent" and "Angiogenesis-driven" molecular subgroups, each associated with a significantly longer OS with atezo+bev vs. sorafenib (p of interaction = 0.027), and a “Resistant” subset. Conclusion Our study unveils two distinct molecular subsets of clinical benefit to atezolizumab plus bevacizumab in advanced HCC (“Immune-competent” and “Angiogenesis-driven”) as well as the main traits of primary resistance to this therapy, thus providing a molecular framework to stratify patients based on clinical outcome and guiding potential strategies to overcome resistance.
- ItemOpen AccessSynergic Integration of the miRNome, Machine Learning and Bioinformatics for the Identification of Potential Disease-Modifying Agents in Obstructive Sleep Apnea(Elsevier, 2025) Belmonte, Thalía; Benítez, Iván; García Hidalgo, María Coronada; Molinero, Marta; Pinilla, Lucía; Minguez Roure, Olga; Vaca, Rafaela; Aguilà, Maria; Moncusí Moix, Anna; Torres, Gerard; Mediano, Olga; Masa, Juan Fernando; Montero-San-Martín, Blanca; Ibarz Escuer, Mercedes; Martinez-Camblor, Pablo; Gómez-Carballa, Alberto; Salas, Antonio; Martinon-Torres, Marcos , Federico; Barbé Illa, Ferran; Sánchez de la Torre, Manuel; de Gonzalo Calvo, DavidIntroduction Understanding the diverse pathogenetic pathways in obstructive sleep apnea (OSA) is crucial for improving outcomes. microRNA (miRNA) profiling is a promising strategy for elucidating these mechanisms. Objective To characterize the pathogenetic pathways linked to OSA through the integration of miRNA profiles, machine learning (ML) and bioinformatics. Methods This multicenter study involved 525 patients with suspected OSA who underwent polysomnography. Plasma miRNAs were quantified via RNA sequencing in the discovery phase, with validation in two subsequent phases using RT-qPCR. Supervised ML feature selection methods and comprehensive bioinformatic analyses were employed. The associations among miRNA targets, OSA and OSA treatment were further explored using publicly available external datasets. Results Following the discovery and technical validation phases in a subset of patients with and without confirmed OSA (n = 53), eleven miRNAs were identified as candidates for the subsequent feature selection process. These miRNAs were then quantified in the remaining population (n = 472). Feature selection methods revealed that the miRNAs let-7d-5p, miR-15a-5p and miR-107 were the most informative of OSA. The predominant mechanisms linked to these miRNAs were closely related to cellular events such as cell death, cell differentiation, extracellular remodeling, autophagy and metabolism. One target of let-7d-5p and miR-15a-5p, the TFDP2 gene, exhibited significant differences in gene expression between subjects with and without OSA across three independent databases. Conclusion Our study identified three plasma miRNAs that, in conjunction with their target genes, provide new insights into OSA pathogenesis and reveal novel regulators and potential drug targets.
- ItemOpen AccessHeterologous Expression of Either Human or Soya Bean Ferritins in Budding Yeast Reveals Common Functions Protecting Against Oxidative Agents and Counteracting Double-Strand Break Accumulation(MDPI, 2025) Pujol Carrión, Núria; Torre Ruiz, M. A. de laFerritins are globular proteins that, upon self-assembly in nanocages, are capable of bio-safely storing huge concentrations of bioavailable iron. They are present in most cell types and organisms; one of the exceptions is yeast. Heterologous expression of either human or vegetal ferritins in Saccharomyces cerevisiae revealed new and unknown functions for soya bean ferritins; validated this model by confirming previously characterized functions in human ferritins and also demonstrated that, like human H chain, vegetal H1, and H2 chains also shown a tendency to localize in the nucleus when expressed in an eukaryotic cell model lacking plastids and chloroplasts. Furthermore, when expressed in the system budding yeast, the four ferritins (human H and L and soya bean H1 and H2 chains) present equivalent and relevant functions as protectors against oxidative damage and against the accumulation of double-strand breaks in the DNA. We present evidence demonstrating that these effects are exclusively observed with oxidative agents that operate through the Fenton reaction, such as H2O2. Here, we also discuss the ferritin requirement for N-glycosylation to exert these functions. We believe that our approach might contribute to extending the knowledge around ferritin function and its consequent relevance to human health.
- ItemOpen AccessMammalian TatD DNase domain containing 1 (TATDN1) is a proteostasis-responsive gene with roles in ventricular structure and neuromuscular function(John Wiley & Sons, 2025) Barés Junqué, Gisel; Beà Tàrrega, Aida; Sancho-Balsells, Anna; Valero, Juan G.; Aluja, David; Inserte Igual, Javier; García Carpi, Sandra; Miró-Casas, Elisabet; Borràs-Pernas, Sara; Hernández i Estanyol, Sara; Martínez-Val, Ana; Olsen, Jesper V.; Tebar, Francesc; Cañas, Xavier; Comella i Carnicé, Joan Xavier; Pérez Galán, Patricia; Ruiz Meana, Marisol; Giralt, Albert; Llovera i Tomàs, Marta; Sanchis, DanielThe characterization of highly conserved but poorly understood genes often reveals unexpected biological roles, advancing our understanding of disease mechanisms. One such gene is Mammalian TatD DNase domain containing 1 (Tatdn1), the mammalian homolog of bacterial Twin-arginine translocation D (TatD), a protein proposed to have roles either in DNA degradation or protein quality control in unicellular organisms. Despite its association with different pathologies, including several cancer types and cardiovascular diseases, the role of TATDN1 in mammals remains unexplored. Here, we demonstrate that Tatdn1 encodes a cytoplasmic protein that does not participate in DNA degradation but is upregulated in cells under proteostasis stress. Tatdn1-deficient mice exhibit dysregulated expression of genes involved in membrane and extracellular protein biology, along with mild dilated cardiomyopathy and impaired motor coordination. These findings identify TATDN1 as a key player in cytosolic processes linked to protein homeostasis, with significant physiological implications for cardiac and neurological function.