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Characterization and comparative profiling of piRNAs in serum biopsies of pediatric Wilms tumor patients

cancer Cell International 2025年第1期25卷 1-15页

作者： Mohamed, Fatma S. Jalal, Deena Fadel, Youssef M. El-Mashtoly, Samir F. Khaled, Wael Z. Sayed, Ahmed A. Ghazy, Mohamed A. Biotechnology Program Institute of Basic and Applied Science Egypt-Japan University of Science and Technology Alexandria New Borg El-Arab City Egypt Biochemistry ProgramFaculty of Science Minia University El-Minia Egypt Genomics and Metagenomics Program Department of Basic Research Children’s Cancer Hospital Egypt Cairo 57357 Egypt Bioinformatics Group Center for Informatics Science School of Information Technology and Computer Science Nile University Giza Egypt Leibniz Institute of Photonic Technology Albert Einstein-Straße 9 Jena 07745 Germany Department of Pediatric Oncology National Cancer Institute Cairo Egypt Department of Pediatric Oncology Children’s Cancer Hospital Egypt Cairo 57357 Egypt Consultant Pediatric Oncology Mouwasat Hospital Dammam Saudi Arabia Department of Biochemistry Faculty of Science Ain Shams University Cairo Egypt

Piwi-interacting RNAs (piRNAs) are small non-coding RNAs involved in transposon silencing and linked to cancer progression. However, their role in Wilms tumors (WT) remains unexplored. We conducted a thorough analysis and characterization of piRNAs in serum liquid biopsies of WT patients. Our study examined their expression patterns and functional annotations related to WT pathogenesis, as well as their clinical potential for diagnosis and monitoring. We identified 307 piRNAs expressed in WT serum samples, with 4% classified as repeat-related and 96% as non-repeat-related. The most abundant repeat-related piRNAs originated from LINEs retrotransposon, while tRNA-derived piRNAs were the most prevalent among non-repeat-related piRNAs. Furthermore, a distinct profile of 34 piRNAs showed significant differential expression in WT patients compared to healthy controls—22 downregulated and 12 upregulated. The target genes of differentially expressed piRNAs exhibited significant enrichment in biological pathways related to cytokine activity, inflammatory responses, TGF-beta signaling, p38 MAPK, and ErbB signaling. These genes are also involved in DNA damage response, DNA methylation, cell cycle regulation, as well as kidney development and function. Low expression levels of several piRNAs, especially piR-hsa-1,913,711, piR-hsa-28,190, piR-hsa-28,849, piR-hsa-28,848, and piR-hsa-28,318, showed significant diagnostic potential as non-invasive biomarkers for WT (AUC > 0.8, p < 0.05). Their expression levels also significantly correlated with adverse pathological features, including metastasis, anaplasia, and bilateral WT development. In conclusion, non-transposon-related piRNAs may serve as reliable biomarkers for WT and possess potential non-germline functions, particularly in regulating DNA methylation, cell growth, immune responses, and immune responses. Further studies are warranted to elucidate their functional significance. © The Author(s) 2025.

关键词： Blood-based biomarkers Diagnostic potential Non-germline functions Non-transposon-related PiRNAs PiRNAome profiling Wilms tumor

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DLBclass: a probabilistic molecular classifier to guide clinical investigation and practice in diffuse large B-cell lymphoma

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Blood 2025年第18期145卷 2041-2055页

作者： Chapuy, Björn Wood, Timothy Stewart, Chip Dunford, Andrew Wienand, Kirsty Khan, Sumbul Jawed Serin, Nazli Wang, Meng Calabretta, Eleonora Shimono, Joji Van Seters, Samantha Wisemann, Sam Belkin, Saveliy Heimann, David Redd, Robert Shipp, Margaret A. Getz, Gad Department of Medical Oncology Dana-Farber Cancer Institute Boston MA United States Harvard Medical School Boston MA United States Department of Hematology Oncology and Cancer Immunology Campus Benjamin Franklin Charité-Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin Berlin Germany Cancer Program Broad Institute of Massachusetts Institute of Technology and Harvard Cambridge MA United States Department of Biostatistics and Computational Biology Dana-Farber Cancer Institute Boston MA United States Krantz Family Center for Cancer Research and Department of Pathology Massachusetts General Hospital Boston MA United States German Cancer Consortium partner site Berlin a partnership between German Cancer Consortium and Charité-Universitätsmedizin Berlin Berlin Germany

Diffuse large B-cell lymphoma (DLBCL) is a clinically and molecularly heterogeneous disease. The increasing recognition and targeting of genetically defined DLBCLs highlight the need for robust classification algorithms. We previously characterized recurrent genetic alterations in DLBCL and identified 5 discrete subtypes, clusters 1 to 5 (C1-C5), with unique mechanisms of transformation, immune evasion, candidate treatment targets, and different outcomes after standard first-line therapy. Herein, we validate the C1 to C5 DLBCL taxonomy in an independent data set and use the expanded series of 699 primary DLBCLs to develop a probabilistic molecular classifier and confirm its performance in an independent test set. Using our previously assigned cluster labels as a reference, we systematically compared multiple machine learning models and strategies for input feature dimensionality reduction with a newly developed performance metric that captured the relationship between accuracy and confidence of class assignments. The winning neural network model, DLBclass, assigned all cases in the training/validation and independent test sets with 91% and 89% accuracies, respectively. In the 75% of cases with confidence >0.7, DLBclass assignments were accurate in 97% of the training/validation set and 98% of the test set. DLBclass enables robust prospective classification of single cases for inclusion in genetically guided clinical trials or practice and represents a framework for the development of genomics-based classification methods in other cancers. © 2025 American Society of Hematology

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Hallmarks of ovarian aging

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Trends in Endocrinology and Metabolism 2025年第5期36卷 418-439页

作者： Wu, Chuqing Chen, Dan Stout, Michael B. Wu, Meng Wang, Shixuan Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Hubei Wuhan 430030 China National Clinical Research Center for Obstetrical and Gynecological Diseases Hubei Wuhan 430030 China Key Laboratory of Cancer Invasion and Metastasis Ministry of Education Hubei Wuhan 430030 China Aging and Metabolism Research Program Oklahoma Medical Research Foundation Oklahoma City OK United States Oklahoma City Veterans Affairs Medical Center Oklahoma City OK United States

Ovarian aging is considered to be the pacemaker of female aging, and is linked to various comorbidities such as osteoporosis, cardiovascular diseases, and cognitive decline. Many efforts have been made to determine the mechanisms underlying ovarian aging, but their potential to act as hallmarks to predict and intervene in this process currently remains unclear. In this review we propose nine hallmarks as common features of ovarian aging: genomic instability, telomere attrition, epigenetic alterations, impaired autophagy, cellular senescence, deregulated nutrient-sensing, mitochondrial dysfunction, oxidative stress, and chronic inflammation. Understanding the interaction between these hallmarks poses a significant challenge but may also pave the way to the identification of pharmaceutical targets that can attenuate ovarian aging. © 2025 Elsevier Ltd

关键词： endocrine fertility hallmarks oocyte ovarian aging

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Novel Genetic Risk Variants Associated with Oral Tongue Squamous Cell Carcinoma

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Head and Neck Pathology 2025年第1期19卷 45-45页

作者： Nikkilä, Rayan Mäkitie, Antti Joensuu, Heikki Markkanen, Saara Elenius, Klaus Monni, Outi Palotie, Aarno Saarentaus, Elmo Salo, Tuula Bizaki-Vallaskangas, Argyro Department of Otorhinolaryngology - Head and Neck Surgery University of Helsinki and HUS Helsinki University Hospital Helsinki Finland Finnish Cancer Registry Institute for Statistical and Epidemiological Cancer and Research Helsinki Finland Research Program in Systems Oncology Faculty of Medicine University of Helsinki Helsinki Finland Department of Oncology HUS Helsinki University Hospital and University of Helsinki Helsinki Finland Department of Otolaryngology Faculty of Medicine and Health Technology Tampere University Tampere Finland The Wellbeing Services County of Pirkanmaa Tampere Finland Institute of Biomedicine and MediCity Research Laboratory University of Turku Turku Finland Turku Bioscience Centre University of Turku and Åbo Akademi University Turku Finland Department of Oncology Turku University Hospital Turku Finland iCAN Digital Precision Cancer Medicine Flagship University of Helsinki Helsinki Finland Applied Tumor Genomics Research Program Faculty of Medicine University of Helsinki Helsinki Finland Institute for Molecular Medicine Finland and the Helsinki Institute of Life Science University of Helsinki Helsinki Finland The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics The Broad Institute of MIT and Harvard Cambridge MA United States Analytic and Translational Genetics Unit Department of Medicine Department of Neurology and Department of Psychiatry Massachusetts General Hospital Boston MA United States Department of Oral and Maxillofacial Diseases University of Helsinki Helsinki Finland Translational Immunology Research Program Faculty of Medicine University of Helsinki Helsinki Finland Department of Pathology HUS Helsinki University Hospital Helsinki Finland Research Unit of Population Health Faculty of Medicine University of Oulu Oulu Finland Medical Research Center Oulu University Hospital Oulu Finland

Purpose: Limited data from genome-wide association studies (GWAS) focusing on oral tongue squamous cell carcinoma (OTSCC) are available. The present study was conducted to explore genetic associations for OTSCC. Methods: A GWAS on 376 cases of OTSCC was conducted using the FinnGen Data Freeze-12 dataset. The case-cohort included 205 males and 171 females. Cases with malignancies involving the base of the tongue or lingual tonsil were excluded from the case-cohort. Individuals with no recorded history of malignancy were used as controls (n = 407,067). A Phenome-wide association study (PheWAS) was performed for the lead variants to assess their co-associations with other cancers. Results: GWAS analysis identified three genome-wide significant loci associated with OTSCC (p < 5 × 10–8), located at 5p15.33 (rs27067 near gene LINC01511), 10q24 (rs1007771191 near RPS3AP36), and 20p12.3 (rs1438070080 near PLCB1), respectively. PheWAS showed associations of rs27067 mainly with prostate cancer (OR = 1.06, p = 5.41 × 10^–7), and seborrheic keratosis (OR = 1.11, p = 1.51 × 10^–11). A co-directional effect with melanoma was also observed (OR = 0.93, p = 6.24 × 10^–5). Conclusion: The GWAS detected two novel genetic associations with OTSCC. Further research is needed to identify the genes at these loci that contribute to the molecular pathogenesis of OTSCC. © The Author(s) 2025.

关键词： FinnGen Genetic variant Genome-wide association Single nucleotide polymorphism Tongue cancer

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Nanoparticles may influence mast cells gene expression profiles without affecting their degranulation function

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Nanomedicine: Nanotechnology, Biology, and Medicine 2025年 66卷 102818-102818页

作者： Newton, Hannah S. Cedrone, Edward Grunberger, Jason Xie, Shaojun Zhao, Yongmei Tran, Bao Toms, Bradley S. Xu, Weining Plant-Hately, Alexander Liptrott, Neill J. Dobrovolskaia, Marina A. Nanotechnology Characterization Lab. Cancer Research Technology Program Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute FrederickMD21702 United States Utah Center for Nanomedicine Department of Molecular Pharmaceutics University of Utah Salt Lake CityUT United States Sequencing Facility Bioinformatics Group Biomedical Informatics and Data Science Directorate Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute FrederickMD21702 United States CCR Sequencing Facility Cancer Research Technology Program Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute FrederickMD21702 United States 10x Genomics Inc. PleasantonCA94588-3260 United States Immunocompatibility Group Department of Pharmacology and Therapeutics Institute of Systems Molecular and Integrative Biology University of Liverpool LiverpoolL7 3NY United Kingdom Institute of Systems Molecular and Integrative Biology University of Liverpool LiverpoolL7 8TX United Kingdom

An in vitro method for monitoring nanoparticle effects on IgE-dependent mast cell degranulation was developed and validated. The assayed nanoparticles included four clinical-grade nanomedicines (Abraxane, Doxil, AmBisome, and Feraheme) and three commercial research-grade nanomaterials (generation 5 PAMAM dendrimers with carboxy-, hydroxy-, or amine- surface functionalities). Most of the tested materials did not alter IgE-dependent mast cell degranulation, suggesting that nanoparticles and nanomedicines are unlikely to worsen pre-existing allergies to other antigens. Two clinical-grade formulations containing cytotoxic oncology drugs—Abraxane and Doxil—decreased degranulation. Abraxane but not Doxil decreased FcΕR expression on the cell surface. Single-cell sequencing revealed the most differentially expressed genes (DEG) in Abraxane and Doxil-treated cultures. Interestingly, Feraheme and amine-terminated dendrimers induced DEG without affecting degranulation. These data demonstrate that some nanomaterials have more effects on immune cells than can be detected by a functional immunoassay. © 2025 Elsevier Inc.

关键词： Nanoclay

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Survey of radiation therapists’ current practices and perceptions of psychosocial and supportive care in Canada and Norway

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Supportive Care in cancer 2025年第5期33卷 1-12页

作者： Bezanson, Sophie Aas, Espen Smith, Kerry-Ann Di Prospero, Lisa Velec, Michael Ruco, Arlinda Johansen, Safora Interdisciplinary Health Program St. Francis Xavier University Antigonish Canada Department of Life Sciences and Health Oslo Metropolitan University Oslo Norway Collaborative Academic Practice University Health Network Toronto Canada Practice-Based Research and Innovation Sunnybrook Health Sciences Centre Toronto Canada Princess Margaret Cancer Centre University Health Network Toronto Canada Department of Radiation Oncology University of Toronto Toronto Canada Peter Gilgan Centre for Women’s Cancers Women’s College Hospital Toronto Canada Beatrice Hunter Cancer Research Institute Dalhousie University Halifax Canada Nova Scotia Health Halifax Canada VHA Home HealthCare Toronto Canada Department of Cancer Treatment Oslo University Hospital Oslo Norway Health and Social Science Cluster Singapore Institute of Technology Singapore Singapore

Purpose: Many cancer patients undergoing radiation therapy report unmet psychosocial needs, which can negatively impact their treatment outcomes and quality of life. This study explored the current practices and perceptions of radiation therapists (RTs) practicing in Canada and Norway with respect to addressing the psychosocial and supportive care (PSSC) needs of their patients. Methods: A cross-sectional study was conducted using an online evidence-informed survey of RTs in Canada and Norway that focused on (1) demographics, (2) RTs’ confidence level and perceptions related to PSSC, and (3) RTs’ current practices related to PSSC. Descriptive statistics, chi-square tests, and Mann–Whitney U tests were used to summarize the sample and compare differences between countries. Results: A total of 210 RTs completed the survey (Canada, n = 79;Norway, n = 131). RTs in both countries identified PSSC as an important aspect of quality care. Canadian RTs expressed a greater desire to expand their scope of practice in PSSC (p = 0.001). Norwegian RTs reported spending more time providing PSSC (mean: 8.3 h vs. 3.8 h;p < 0.001) and were satisfied with their current capacity. Barriers common to both countries included a lack of training and time constraints. Canadian RTs additionally reported limited institutional support. Conclusion: Significant differences exist in the current practices and perceptions of RTs in Canada and Norway regarding PSSC delivery. However, Canadian and Norwegian RTs agree that engaging in PSSC ensures the best care for patients undergoing radiation therapy. With enhanced training, knowledge translation of resources, and institutional support, RTs can better address the PSSC needs of their patients. © The Author(s) 2025.

关键词： cancer Psychosocial oncology Radiation therapists Supportive care

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BPS2025 - Biophysical characterization of small molecule inhibitors binding to KRAS

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Biophysical Journal 2025年第3期124卷 177a-177a页

作者： Andrew G. Stephen Patrick Alexander Monalisa Swain Dana Rabara Erik K. Larsen Cancer Research Technology Program Frederick National Laboratory for Cancer Research Frederick MD USA

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From rare to more common: The emerging role of omics in improving understanding and treatment of severe inflammatory and hyperinflammatory conditions

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Journal of Allergy and Clinical Immunology 2025年第5期155卷 1435-1450页

作者： Keskitalo, Salla Seppänen, Mikko R.J. del Sol, Antonio Varjosalo, Markku Institute of Biotechnology Helsinki Institute of Life Science HiLIFE University of Helsinki Helsinki Finland Pediatric Research Center New Children's Hospital University of Helsinki and HUS Helsinki University Hospital Helsinki Finland Translational Immunology Research Program University of Helsinki Helsinki Finland European Reference Network Rare Immunodeficiency Autoinflammatory and Autoimmune Diseases Network (ERN RITA) Core Center Utrecht Netherlands Computational Biology Group Luxembourg Centre for Systems Biomedicine (LCSB) University of Luxembourg Esch-sur-Alzette Luxembourg Computational Biology Group Basque Research and Technology Alliance (CIC bioGUNE-BRTA) Derio Spain Ikerbasque Basque Foundation for Science Bilbao Spain Department of Biochemistry and Developmental Biology and Translational Cancer Medicine Program Faculty of Medicine University of Helsinki Finland Helsinki Finland

Inflammation is a pathogenic driver of many diseases, including atherosclerosis and rheumatoid arthritis. Hyperinflammation can be seen as any inflammatory response that is deleterious to the host, regardless of cause. In medicine, hyperinflammation is defined as severe, deleterious, and fluctuating systemic or local inflammation with presence of a cytokine storm. It has been associated with rare autoinflammatory disorders. However, advances in omics technologies, including genomics, proteomics, and metabolomics, have revealed it to be more common, occurring in sepsis and severe coronavirus disease 2019. With a focus on proteomics, this review highlights the key role of omics in this shift. Through an exploration of research, we present how omics technologies have contributed to improved diagnostics, prognostics, and targeted therapeutics in the field of hyperinflammation. We also discuss the integration of advanced technologies, multiomics approaches, and artificial intelligence in analyzing complex datasets to develop targeted therapies, and we address their potential for revolutionizing the clinical aspects of hyperinflammation. We emphasize personalized medicine approaches for effective treatments and outline challenges, including the need for standardized methodologies, robust bioinformatics tools, and ethical considerations regarding data privacy. This review aims to provide a comprehensive overview of the molecular mechanisms underpinning hyperinflammation and underscores the potential of omics technologies in enabling successful clinical management. © 2025 The Authors

关键词： artificial intelligence biomarker discovery cytokine storm genomics Hyperinflammation inflammation metabolomics multiomics omics technologies proteomics

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Nutritional profile of the diet according to circadian clock genes in the European Prospective Investigation into cancer and Nutrition (EPIC) chronodiet study

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Clinical Nutrition 2025年 49卷 165-177页

作者： Molina-Montes, Esther Rodríguez-Barranco, Miguel Alcalá-Santiago, Ángela Gálvez-Navas, José María Huerta, José María Amiano, Pilar Lasheras, Cristina Moreno-Iribas, Conchi Jimenez-Zabala, Ana Chirlaque, María-Dolores Gasque, Alba Luján-Barroso, Leila Agudo, Antonio Jakszyn, Paula Quirós, José Ramón Sánchez, María José Department of Nutrition and Food Science University of Granada Granada Spain Institute of Nutrition and Food Technology (INYTA) ‘José Mataix’ Biomedical Research Centre University of Granada Granada Spain Instituto de Investigación Biosanitaria ibs.GRANADA Granada Spain CIBER of Epidemiology and Public Health (CIBERESP) Madrid Spain Andalusian School of Public Health (EASP) Granada Spain Department of Epidemiology Murcia Regional Health Council-IMIB Murcia Spain Ministry of Health of the Basque Government Sub Directorate for Public Health and Addictions of Gipuzkoa San Sebastian Spain Biodonostia Health Research Institute Epidemiology of Chronic and Communicable Diseases Group San Sebastián Spain Functional Biology Department School of Medicine University of Oviedo Asturias Spain Navarra Public Health Institute Pamplona Spain Navarra Institute for Health Research (IdiSNA) Pamplona 31008 Spain University of Murcia Murcia Spain Unit of Nutrition and Cancer Catalan Institute of Oncology - ICO Nutrition and Cancer Group Epidemiology Public Health Cancer Prevention and Palliative Care Program Bellvitge Biomedical Research Institute - IDIBELL L'Hospitalet de Llobregat Spain Blanquerna Health Sciences Faculty Ramon Llull University Barcelona 08022 Spain Public Health Directorate Asturias Spain

Background & aims: Circadian rhythms seem to impact both dietary intake and metabolism, depending on the individual's chronotype. We aimed to explore whether the nutritional composition of meals throughout the day is influenced by genetics linked to the circadian clock and chronotype within the “European Prospective Investigation into cancer and Nutrition (EPIC) chronodiet” study. Methods: The study population comprised 3,183 subjects with information on diet and twelve genetic variants of six genes (PER1, PER2, PER3, CRY1, NR1D1, CLOCK). The associations between the variants with chrononutrition variables (macronutrients and serving sizes of each meal) were evaluated using linear regression, considering an additive genetic model, and adjusting for sex, age and center, among others. The β coefficients, 95 % confidence intervals (CI), and p-values corrected for multiple comparisons were estimated. A genetic risk score (GRS) that was associated to the evening/late chronotype as well as overweight/obesity in a previous study, the chronotype-GRS, was tested for its association with chrononutrition variables. Results: The nutritional profile of the diet differed according to the individual's chronotype, with evening/late chronotypes exhibiting an unbalanced intake during breakfast and dinner compared to the intermediate and early chronotypes (e.g., percentage of fats consumed at breakfast relative to the total fat intake: 13 % and 9 %, respectively). However, significant differences were not encountered by the chronotype-GRS. In multivariate analyses, individual associations between the genetic variants and the nutrients revealed some nominal associations (e.g., rs1801260 and rs2070062 with carbohydrates at breakfast: β = −0.06 to 0.08). Higher scorings of the chronotype-GRS were inversely associated with the intake of proteins and carbohydrates (β = −0.46 and −0.41;nominal p-value<0.006;corrected = 0.25) during breakfast. Also, there was an inverse association between t

关键词： Anthropometry Chronobiology Circadian clock Diet habits Genetic association analyses Nutrition

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Library-based single-cell analysis of CAR signaling reveals drivers of in vivo persistence

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Cell Systems 2025年第5期16卷 101260页

作者： Perez, Caleb R. Garmilla, Andrea Nilsson, Avlant Baghdassarian, Hratch M. Gordon, Khloe S. Lima, Louise G. Smith, Blake E. Maus, Marcela V. Lauffenburger, Douglas A. Birnbaum, Michael E. Koch Institute for Integrative Cancer Research Cambridge MA United States Department of Biological Engineering Massachusetts Institute of Technology Cambridge MA United States Singapore-MIT Alliance for Research and Technology Centre Singapore Singapore Program in Immunology Harvard Medical School Boston MA United States Department of Biology and Biological Engineering Chalmers University of Technology Gothenburg Sweden Kranz Family Center for Cancer Research and Cellular Immunotherapy Program Massachusetts General Hospital Charlestown MA United States Department of Medicine Harvard Medical School Boston MA United States Ragon Institute of MIT MGH and Harvard Cambridge MA United States

The anti-tumor function of engineered T cells expressing chimeric antigen receptors (CARs) is dependent on signals transduced through intracellular signaling domains (ICDs). Different ICDs are known to drive distinct phenotypes, but systematic investigations into how ICD architectures direct T cell function—particularly at the molecular level—are lacking. Here, we use single-cell sequencing to map diverse signaling inputs to transcriptional outputs, focusing on a defined library of clinically relevant ICD architectures. Informed by these observations, we functionally characterize transcriptionally distinct ICD variants across various contexts to build comprehensive maps from ICD composition to phenotypic output. We identify a unique tonic signaling signature associated with a subset of ICD architectures that drives durable in vivo persistence and efficacy in liquid, but not solid, tumors. Our findings work toward decoding CAR signaling design principles, with implications for the rational design of next-generation ICD architectures optimized for in vivo function. © 2025 Elsevier Inc.

关键词： CAR T cells chimeric antigen receptors immunotherapy intracellular signaling domains persistence pooled screens single-cell RNA sequencing T cell signaling T cells tonic signaling

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