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Molecular Interplay Between Non-Coding RNAs and Connexins and Its Possible Role in Cancer
(MDPI AG, 2025-03-12)
Pablo Pérez-Moreno
;
Juan P. Muñoz
;
RETAMAL LUCERO, MAURICIO ANTONIO
Non-coding RNAs (ncRNAs) are sequences that do not encode for proteins and play key roles in different cellular processes, including cell proliferation and differentiation. On the other hand, connexins (Cxs) are transmembrane proteins that principally allow intercellular communication. In pathological conditions such as cancer, there is a deregulation in the expression and/or function of ncRNAs and Cxs, which in turn leads to an enhancement in the aggressive phenotype, such as a greater proliferative and invasive capacity. This suggests a plausible interplay between ncRNAs and Cxs. Based on that, this review aims to summarize the current knowledge regarding this relationship and to analyze how it may influence the development of aggressive traits in cancer cells and the clinicopathological features of cancer patients. Finally, we discuss the potential of ncRNAs and Cxs as promising clinical biomarkers for cancer diagnosis, prognosis, and therapeutic targeting.
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Developing and Validating an Automatic Support System for Tumor Coding in Pathology Reports in Spanish
(American Society of Clinical Oncology (ASCO), 2025-02)
Fabián Villena
;
Pablo Báez
;
Sergio Peñafiel
;
Matías Rojas
;
Inti Paredes
Purpose Pathology reports provide valuable information for cancer registries to understand, plan, and implement strategies to mitigate the impact of cancer. However, coding essential information from unstructured reports is performed by experts in a time-consuming manual process. We developed and validated a novel two-step automatic coding system that first recognizes tumor morphology and topography mentions from free text and then suggests codes from the International Classification of Diseases for Oncology (ICD-O) in Spanish. Materials and Methods We created an annotated corpus of tumor morphology and topography mentions consisting of 1,101 documents. We combined it with the CANTEMIST corpus (Cancer Text Mining Shared Task). Specifically, we implemented a named entity recognition (NER) model using the bidirectional long short-term memory network-conditional random field architecture enhanced with a stacked embedding layer. We applied transfer learning from state-of-the-art pretrained language models to obtain high-quality contextual representations, thus improving the detection of entities. The mentions found using this model were subsequently oded using a search engine tailored to the ICD-O codes. Results Our NER models achieved an F1 score of 0.86 and 0.90 for tumor morphology and topography, respectively. The overall performance of our automatic coding system achieved an accuracy at five suggestions of 0.72 and 0.65 for tumor morphology and topography, respectively. Conclusion These results demonstrate the feasibility of implementing natural language processing tools in the routine of a cancer center to extract and code valuable information from pathology reports. Our recommender system allows reliable and transparent coding at the moment of consultation. This publication shares the annotated corpus in Spanish, annotation guidelines, and source code to reproduce our experiments.
Scopus© Citations 3 1
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A case report of sarcoidosis and ulcerative colitis: overlap or coexistence
(Sociedad Espanola de Patologia Digestiva (SEPD), 2024)
Alex Fabián Arenas Aravena
;
Diego Ruedi
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Matías Sanhueza
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IBAÑEZ VODNIZZA, SEBASTIAN EDUARDO
;
Gonzalo Carrasco-Avino
4
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Retrospective study on disparities in time-to-treatment by health insurance system in Chilean breast cancer patients
(Medwave Estudios Limitada, 2025-04-10)
ACEVEDO ROMO, JOHANNA PATRICIA
;
Teresa Ip
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Lea Maureira
;
Cesar Sanchez
;
Claudia Osorio
Introduction Breast cancer is the most common malignancy in the Americas, and the second leading cause of cancer death. Disparities in the time to treatment can significantly impact patient outcomes and typically affect lower socioeconomic individuals and/or ethnic minorities. Our study sought to evaluate disparities in time to treatment at three health institutions in Chile according to their type of health insurance (public or private). Methods Our study analyzed a database of breast cancer patients diagnosed between 2017 and 2018. Analyses included descriptive statistics and a linear regression model that incorporated clinical and demographic variables. Additionally, using a proportional risks model, we analyzed the association between clinical variables and mortality. Results Public health insurance (National Health Fund, FONASA) was associated with longer time-to-treatment and extended treatment times versus private health insurance (Social Security Institutions, ISAPRE; p < 0.0001). As expected, a more advanced stage at diagnosis was associated with lower survival. Our proportional risks model found that age was a predictor of breast cancer mortality in stage II patients. Also, total treatment time significantly increased the risk of breast cancer mortality in stage I patients. Conversely, total treatment time did not affect mortality on stages II or III. Conclusions We found significant disparities in the time to treatment of Chilean breast cancer patients using FONASA versus private ISAPRE. FONASA patients experience delays in the initiation of treatment and longer total treatment times compared to their private insurance counterparts. Finally, longer time-to-treatment was associated with more advanced stages and increased mortality.
3
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Connexin46 in the nucleus of cancer cells: a possible role as transcription modulator
(Springer Science and Business Media LLC, 2025-03-27)
Ainoa Fernández-Olivares
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Viviana P Orellana
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Jesús Llanquinao
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NUÑEZ VASQUEZ, GONZALO ESTEBAN
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Pablo Pérez-Moreno
Scopus© Citations 1 10
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Paw Skin as a Translational Model for Investigating Fibrotic and Inflammatory Wound Healing Defects in Recessive Dystrophic Epidermolysis Bullosa
(MDPI AG, 2025-04-30)
DE GREGORIO CONCHA, CRISTIAN ALEJANDRO
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Giselle Ramos-Gonzalez
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Bernardo Morales-Catalán
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EZQUER, EDUARDO FERNANDO
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EZQUER, EDUARDO MARCELO
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genetic disease caused by COL7A1 mutations. It leads to skin fragility, chronic inflammation, and impaired wound healing. The condition often results in fibrotic scarring, pseudosyndactyly, and cutaneous squamous cell carcinoma (SCC). However, current animal models fail to fully replicate chronic RDEB wounds. In this study, we used Collagen VII-hypomorphic mice (Col7a1flNeo/flNeo) and created full-thickness wounds on their paw skin, an area prone to fibrosis due to mechanical stress. We analyzed the healing process using histology, immunofluorescence, and electron microscopy. The RDEB mice showed delayed wound closure, increased inflammation, and poor granulation tissue formation. At 30 days post-injury, we observed persistent fibrosis, with elevated levels of Collagen I, α-SMA+ myofibroblasts, and tenascin-C. These mice also had fewer intraepidermal nerve fibers, which may help explain the neuropathic pain associated with RDEB. Our model reproduces the main features of chronic RDEB wounds. It offers a useful tool for evaluating therapies aimed at reducing inflammation, fibrosis, and tumor risk in these patients.
Scopus© Citations 3 4
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White matter volume and microstructural integrity are associated with fatigue in relapsing multiple sclerosis
(Springer Science and Business Media LLC, 2025-05-12)
FIGUEROA VARGAS, ALEJANDRA MABEL
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Sebastián Navarrete-Caro
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Claudia Cárcamo
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Ethel Ciampi
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Macarena Vásquez-Torres
10
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Methylated Reprimo Cell-Free DNA as a Non-Invasive Biomarker for Gastric Cancer
(MDPI AG, 2025-04-03)
María José Maturana
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Oslando Padilla
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Pablo M. Santoro
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Maria Alejandra Alarcón
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Wilda Olivares
Restrictions resulting from the COVID-19 pandemic abruptly reversed the slow decline of the diagnosis and mortality rates of gastric cancer (GC). This scenario highlights the importance of developing cost-effective methods for mass screening and evaluation of treatment response. In this study, we evaluated a non-invasive method based on the circulating methylated cell-free DNA (cfDNA) of Reprimo (RPRM), a tumor suppressor gene associated with the development of GC. Methylated RPRM cfDNA was analyzed in three de-identified cohorts: Cohort 1 comprised 81 participants with GC and 137 healthy donors (HDs); Cohort 2 comprised 27 participants with GC undergoing gastrectomy and/or chemotherapy analyzed at the beginning and after three months of treatment; and Cohort 3 comprised 1105 population-based participants in a secondary prevention program who underwent esophagogastroduodenal (EGD) endoscopy. This cohort includes 180 normal participants, 845 participants with premalignant conditions (692 with chronic atrophic gastritis [AG] and 153 with gastric intestinal metaplasia/low-grade dysplasia [GIM/LGD]), 21 with high-grade dysplasia/early GC [HGD/eGC], and 59 with advanced GC [aGC]). A nested case-control substudy was performed using a combination of methylated RPRM cfDNA and pepsinogens (PG)-I/II ratio. The dense CpG island of the promoter region of the RPRM gene was bisulfite sequenced and analyzed to develop a fluorescence-based real-time PCR assay (MethyLight). This assay allows the determination of the absolute number of copies of methylated RPRM cfDNA. A targeted sequence of PCR amplicon products confirmed the gastric origin of the plasma-isolated samples. In Cohort 1, the mean value of GCs (32,240.00 copies/mL) was higher than that of the HD controls (139.00 copies/mL) (p < 0.0001). After dividing this cohort into training–validation subcohorts, we identified an area under the curve of 0.764 (95% confidence interval (CI) = 0.683–0.845) in the training group. This resulted in a cut-off value of 87.37 copies/mL (sensitivity 70.0% and specificity 80.2%). The validation subcohort predicted a sensitivity of 66.67% and a specificity of 83.33%. In Cohort 2 (monitoring treatment response), RPRM levels significantly decreased in responders (p = 0.0042) compared to non-responders. In Cohort 3 (population-based participants), 18.9% %, 24.1%, 30.7%, 47.0%, and 71.2% of normal, AG, GIM/LGD, HGD/eGC, and aGC participants tested positive for methylated RPRM cfDNA, respectively. Overall sensitivity and specificity in distinguishing normal/premalignant conditions vs. GC were 65.0% (95% CI 53.52% to 75.33%) and 75.9% (95% CI 73.16% to 78.49%), respectively, with an accuracy of 75.11% (95% CI 72.45% to 77.64%). Logistic regression analyses revealed an OR of 1.85 (95% CI 1.11–3.07, p = 0.02) and an odds ratio (OR) of 3.9 (95% CI 1.53–9.93, p = 0.004) for the risk of developing GIM/LGD and HGD/eGC, respectively. The combined methylated RPRM cfDNA and PG-I/II ratio reached a sensitivity of 78.9% (95% CI 54.43% to 93.95%) and specificity of 63.04% (95% CI 52.34% to 72.88%) for detecting HGD/eGC vs. three to six age- and sex-matched participants with premalignant conditions. Our results demonstrate that methylated RPRM cfDNA should be considered a direct biomarker for the non-invasive detection of GC and a predictive biomarker for treatment response.
1Scopus© Citations 4
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TGFβ links EBV to multisystem inflammatory syndrome in children
(Springer Science and Business Media LLC, 2025-03-12)
Carl Christoph Goetzke
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Mona Massoud
;
Stefan Frischbutter
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Gabriela Maria Guerra
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Marta Ferreira-Gomes
<jats:title>Abstract</jats:title> <jats:p>In a subset of children and adolescents, SARS-CoV-2 infection induces a severe acute hyperinflammatory shock<jats:sup>1</jats:sup> termed multisystem inflammatory syndrome in children (MIS-C) at four to eight weeks after infection. MIS-C is characterized by a specific T cell expansion<jats:sup>2</jats:sup> and systemic hyperinflammation<jats:sup>3</jats:sup>. The pathogenesis of MIS-C remains largely unknown. Here we show that acute MIS-C is characterized by impaired reactivation of virus-reactive memory T cells, which depends on increased serum levels of the cytokine TGFβ resembling those that occur during severe COVID-19 (refs. <jats:sup>4,5</jats:sup>). This functional impairment in T cell reactivity is accompanied by the presence of TGFβ-response signatures in T cells, B cells and monocytes along with reduced antigen-presentation capabilities of monocytes, and can be reversed by blocking TGFβ. Furthermore, T cell receptor repertoires of patients with MIS-C exhibit expansion of T cells expressing TCRVβ21.3, resembling Epstein–Barr virus (EBV)-reactive T cell clones capable of eliminating EBV-infected B cells. Additionally, serum TGFβ in patients with MIS-C can trigger EBV reactivation, which is reversible with TGFβ blockade. Clinically, the TGFβ-induced defect in T cell reactivity correlates with a higher EBV seroprevalence in patients with MIS-C compared with age-matched controls, along with the occurrence of EBV reactivation. Our findings establish a connection between SARS-CoV-2 infection and COVID-19 sequelae in children, in which impaired T cell cytotoxicity triggered by TGFβ overproduction leads to EBV reactivation and subsequent hyperinflammation.</jats:p>
Scopus© Citations 4 2
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A Novel Homozygous 9385 bp Deletion in the FERMT1 (KIND1) Gene in a Malaysian Family with Kindler Epidermolysis bullosa and a Review of Large Deletions
(MDPI AG, 2025-04-29)
Alfred Klausegger
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Fabian Leditzky
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Susanne Krämer
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PALISSON ETCHARREN, FRANCIS
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YUBERO GONCALVEZ, MARIA JOAO
Kindler Epidermolysis bullosa (KEB; OMIM 173650) is a rare autosomal recessive genodermatosis characterized by bullous poikiloderma and photosensitivity. Additional presentations include blistering, poor wound healing, skin atrophy, and increased risk of skin cancer. Most cases of KEB result from aberrations in the FERMT1 (Fermitin family member 1) gene encoding kindlin-1 and include nonsense, frameshift, splicing, and missense variants. Large deletion variants have been reported in nine cases to date. Most variants are predicted to lead to premature termination of translation and to loss of kindlin-1 function. In this study, we report on a 33-year-old male patient who presented with typical clinical manifestations of KEB. As routine molecular testing failed to obtain a diagnosis, Next Generation Sequencing (NGS) of an Epidermolysis Bullosa (EB)-specific panel was carried out followed by the determination of the deletion breakpoints and verification at the mRNA and protein levels. This approach revealed a new large homozygous deletion of ~9.4 kb in the FERMT1 gene involving exons 7 to 9. Finally, we performed a literature review on large FERMT1 deletions. The deletion is predicted to skip exons 7 to 9 within the mRNA, which results in a frameshift. The patient’s phenotype is likely caused by the resulting truncated and non-functioning protein. Our report further enriches the spectrum of FERMT1 gene variants to improve genotype–phenotype correlations.
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