Translational Oncology最新文献

{"title":"Single-cell RNA sequencing reveals palmitoylation-driven cellular heterogeneity and prognostic biomarkers in lung adenocarcinoma","authors":"Taibo Huang ,&nbsp;Lijie Kou ,&nbsp;Qianqian Zhang ,&nbsp;Xueya Liu ,&nbsp;Xingang Hu","doi":"10.1016/j.tranon.2025.102501","DOIUrl":"10.1016/j.tranon.2025.102501","url":null,"abstract":"<div><h3>Background</h3><div>Lung adenocarcinoma (LUAD) is marked by significant variation within tumor cells and continues to be a major global cause of cancer deaths. Palmitoylation is a dynamic lipid-based modification that occurs after protein synthesis and influences the behavior and lifespan of various cancer-related proteins. However, its role in shaping cellular complexity and predicting outcomes in LUAD patients is not yet fully clarified.</div></div><div><h3>Methods</h3><div>We examined single-cell RNA sequencing datasets from LUAD samples to identify distinct malignant cell groups. Palmitoylation-related gene activity was estimated using GSVA and ssGSEA techniques. To further define cellular characteristics, we applied copy number variation mapping, pseudotime progression modeling, transcription factor regulatory scoring, and cell–cell interaction analyses. A 12-gene risk model was developed using marker genes from the cluster (C1) with the most prominent palmitoylation pattern. This model was trained on The Cancer Genome Atlas (TCGA) dataset and confirmed using separate GEO datasets. To evaluate tumor immune context, we analyzed immune cell presence and tumor mutational burden across different risk levels. Laboratory experiments involving both upregulation and silencing of aspartate beta-hydroxylase (ASPH) in LUAD cell cultures were conducted to validate its biological significance.</div></div><div><h3>Results</h3><div>We identified six tumor cell subsets (C0 to C5), with cluster C1 showing peak palmitoylation levels, distinct genomic alterations, and stronger communication with stromal and immune cells. The 12-gene model effectively categorized LUAD patients into high- and low-risk profiles, showing marked survival differences (<em>p</em> &lt; 0.001) and strong performance in time-dependent ROC analysis. Patients in the high-risk group had increased tumor mutational burden and a more immunosuppressive tumor environment. Laboratory findings revealed that raising ASPH expression promoted cell growth, motility, and epithelial–mesenchymal transition. In contrast, reducing ASPH levels triggered cell death and decreased invasiveness.</div></div><div><h3>Conclusions</h3><div>Our single-cell analysis focused on palmitoylation reveals new dimensions of tumor diversity in LUAD and establishes a validated 12-gene risk signature. Functional studies highlight ASPH as a promising candidate for therapeutic targeting. These results deepen our understanding of palmitoylation-associated pathways and present a foundation for both outcome prediction and precision-based treatment strategies in LUAD.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102501"},"PeriodicalIF":5.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor: Prognostic biomarker PSMD14 facilitates bladder cancer tumorigenesis and progression by regulating Nucleolin-YAP1 axis","authors":"Yongzheng Han ,&nbsp;Chang Liu ,&nbsp;Guangzhen Wu","doi":"10.1016/j.tranon.2025.102498","DOIUrl":"10.1016/j.tranon.2025.102498","url":null,"abstract":"","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"61 ","pages":"Article 102498"},"PeriodicalIF":5.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9-mediated PD-1 attenuation enhances tumor infiltrating lymphocyte-based adoptive cellular therapy in humanized-PDX model of hepatocellular carcinoma","authors":"Wu Ge ,&nbsp;Huaping Liu ,&nbsp;Di Wu ,&nbsp;Yang Hu ,&nbsp;Qi Liang ,&nbsp;Muqi Liu ,&nbsp;Hao Liu ,&nbsp;Jianmin Wu ,&nbsp;Juan Zhang ,&nbsp;Yao Deng ,&nbsp;Kedar Ghimire ,&nbsp;Pengfei Rong ,&nbsp;Wei Wang ,&nbsp;Xiaoqian Ma","doi":"10.1016/j.tranon.2025.102484","DOIUrl":"10.1016/j.tranon.2025.102484","url":null,"abstract":"<div><h3>Background</h3><div>Tumor-infiltrating lymphocyte (TIL)-based adoptive cellular therapy (ACT) has become a promising therapeutic approach due to its ability to effectively control disease in multiple types of solid tumor. Antibodies against the negative immune checkpoint programmed cell death protein 1 (PD-1) have been widely used in cancer immunotherapy. We hypothesized that PD-1 depletion in hepatocellular carcinoma (HCC) TIL-derived T cells would enhance their anti-tumor efficacy.</div></div><div><h3>Methods</h3><div>CRISPR/ Cas9 system was employed to target <em>PDCD1</em> in HCC TIL-derived T cells. The phenotypic and functional changes were analyzed by flow cytometry. T-cell receptor (TCR) sequencing and bulk RNA-sequencing of PD-1-edited or non-edited T cells was conducted to examine their differences. Finally, we demonstrated the ability of PD-1-edited or non-edited T cells to inhibit tumor growth in HCC patient-derived xenograft (PDX) models.</div></div><div><h3>Results</h3><div>CRISPR/Cas9 system was demonstrated to provide an effective and stable PD-1-editing efficiency. The phenotypes, effector and memory subpopulations of the PD-1-edited T cells were found to have maintained stability, while they did acquire higher potential in terms of autologous tumor cell elimination. Compared to their counterpart, PD-1-edited T cells also retained a higher level of homology with the whole and tumor-specific TCR clonotypes of primary HCC TILs. Furthermore, PD-1-edited T cells exhibited a superior anti-tumor response compared with non-edited T cells in HCC PDX models.</div></div><div><h3>Conclusion</h3><div>Taken together, our results have provided a foundation for the clinical application of ACT based on genetically modified TIL, offering a new perspective on exploring clinical immunotherapy strategies for HCC, and potentially other solid tumors.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"60 ","pages":"Article 102484"},"PeriodicalIF":5.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KLK5 and KLK7 drive cervical carcinoma via KLK14-dependent RhoA and NF-κB pathways","authors":"Gabriel Viliod Vieira ,&nbsp;Rodrigo Alberto Alves da Silva ,&nbsp;Letícia Andrade Costa ,&nbsp;João Paulo Bianchi Ximenez ,&nbsp;Margarita Lamprou ,&nbsp;Mateus Gonçalves Miranda ,&nbsp;Vitor de Moura Arrais ,&nbsp;Bruna Miyoko Ikenaga de Brito ,&nbsp;Elaine Zayas Marcelino da Silva ,&nbsp;Bruno Belmonte Martinelli Gomes ,&nbsp;Carol Kobori da Fonseca ,&nbsp;Márcia Gaião Alves ,&nbsp;Camila Aparecida Coelho Brazão ,&nbsp;Kevin Luiz Lopes-Delphino ,&nbsp;Laura Miguel Rodríguez ,&nbsp;Thiago Mattar Cunha ,&nbsp;Ana Paula Lepique ,&nbsp;Constantinos M. Mikelis ,&nbsp;Raphael Sanches Peres ,&nbsp;Wilson Araújo Silva Jr ,&nbsp;Katiuchia Uzzun Sales","doi":"10.1016/j.tranon.2025.102488","DOIUrl":"10.1016/j.tranon.2025.102488","url":null,"abstract":"<div><h3>Background</h3><div>The global prevalence of Human Papillomavirus (HPV) infection is approximately 12%, which significantly contributes to the development of cervical cancer as HPV is a key driver of tumorigenesis. However, the precise mechanisms by which HPV promotes carcinogenesis and the involvement of additional components in this process remain poorly understood.</div></div><div><h3>Objective</h3><div>Given the evidence supporting the critical role of serine proteases in carcinogenesis, we investigated their contribution to cervical cancer development in the context of HPV-mediated carcinogenesis.</div></div><div><h3>Methods</h3><div>Human biopsies were analyzed to assess the expression of serine proteases, including matriptase, kallikrein 5 (KLK5), and kallikrein 7 (KLK7), as well as their endogenous inhibitors. Mechanistic studies were conducted using genetically engineered mice, bulk RNA-seq, and reporter assays to elucidate the role of these proteases in HPV-dependent cervical carcinogenesis.</div></div><div><h3>Results</h3><div>Our findings demonstrate increased expression of matriptase, KLK5, and KLK7 in early cervical carcinogenesis. Furthermore, the absence of both KLK5 and KLK7 ameliorates the HPV-dependent phenotype via modulation of KLK14 activation. KLK14 exhibits a pro-tumorigenic effect by regulating PAR-2-dependent RhoA and NF-κB signaling pathways.</div></div><div><h3>Conclusion</h3><div>This study underscores the critical roles of serine proteases KLK5, KLK7, and KLK14 in cervical carcinogenesis, suggesting that these serine proteases are promising targets for the development of novel therapeutic strategies in cervical cancer<strong>.</strong></div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"60 ","pages":"Article 102488"},"PeriodicalIF":5.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HJP 272, an endothelin receptor antagonist, and its role in cancer cell migration and invasion","authors":"Nabeela Baig ,&nbsp;Rameswari Chilamakuri ,&nbsp;Saurabh Agarwal ,&nbsp;Aaron Muth ,&nbsp;Sandra E. Reznik","doi":"10.1016/j.tranon.2025.102492","DOIUrl":"10.1016/j.tranon.2025.102492","url":null,"abstract":"<div><h3>Introduction</h3><div>Endothelins (ETs) are a family of versatile peptides composed of 21 amino acids with three isoforms: ET-1, ET-2, and ET-3. As the most abundant of the three isoforms, ET-1 is involved in various biological processes, such as regulation of vascular tone, humoral homeostasis, and neural crest development. However, focus is now being directed towards investigating the functions of the ET axis in the progression of different tumor types including ovarian, prostate, breast, lungs etc. HJP 272 is a novel ET_AR antagonist and while our group has previously researched its effects on lung inflammation and preterm birth, this study marks the first time its role in cancer has been explored.</div></div><div><h3>Methods</h3><div>We evaluated the <em>in vitro</em> activities of HJP 272 in the ET-1 and ET_AR overexpressing cell lines MDA-MB-231 (TNBC), and A549 (NSCLC). While HJP 272 had no effect on the viability of cancer cells, we observed a significant inhibition in the migration, invasion, and clonogenic capacities of both cell lines. RNA-seq and western blot data demonstrate the potential underlying molecular mechanisms of this compound <em>in vitro</em>. Furthermore, HJP 272 was evaluated in a 3D spheroid assay for its ability to inhibit tumor formation in both cell lines, revealing a significant change in MDA-MB-231 cells while no significant changes were observed in A549 cells.</div></div><div><h3>Conclusions</h3><div>Our work indicates a therapeutic potential for HJP 272 in cancer metastasis. The distinct outcomes between the two cell lines shed light on the potential differences of HJP 272′s effects across multiple cancer types.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"60 ","pages":"Article 102492"},"PeriodicalIF":5.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144781122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin as a promising therapeutic agent for papillary thyroid cancer: Mechanisms of antitumor and pro-apoptotic activity","authors":"Katarzyna Wincenciuk ,&nbsp;Angelika Buczyńska ,&nbsp;Adam Jacek Krętowski ,&nbsp;Agnieszka Adamska","doi":"10.1016/j.tranon.2025.102483","DOIUrl":"10.1016/j.tranon.2025.102483","url":null,"abstract":"<div><div>Metformin, a well-established modulator of various metabolic pathways, including those regulating glucose and lipid metabolism, hormone synthesis, oxidative stress, and apoptosis, has garnered increasing interest in the field of cancer treatment and prevention. Clinical studies have indicated a reduced incidence of cancer in patients with type 2 diabetes mellitus who were treated with metformin. Emerging research has illuminated the underlying antitumor mechanisms of metformin, primarily through its activation of AMP-activated protein kinase (AMPK) and the concomitant inhibition of the mammalian target of rapamycin (mTOR) pathway. These molecular events culminate in the induction of apoptosis. Notably, investigations involving human papillary thyroid cancer (PTC) cells have demonstrated metformin's antimitogenic activity, which is closely linked to its ability to inhibit cellular proliferation and metastasis. Given the rising incidence of PTC in recent decades, there is an urgent need to explore innovative and minimally invasive treatment strategies. Consequently, the exploration of metformin as an adjunctive therapy for PTC has become a topic of critical importance, as it has the potential to effectively impede tumor cell proliferation and promote apoptosis. However, it is important to recognize the current limitations in the evidence supporting the anticancer properties of metformin. Most findings stem from <em>in vitro</em> studies, which may not fully capture the complexities of human physiology. Therefore, the primary objective of this literature review is to comprehensively synthesize recent advancements regarding metformin's anticancer and proapoptotic effects, with particular emphasis on its role in ongoing clinical trials targeting PTC intervention.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"60 ","pages":"Article 102483"},"PeriodicalIF":5.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timosaponin AIII inhibits gastric cancer by causing oxidative stress and blocking autophagic flux","authors":"Chunyang Zhu ,&nbsp;Shuming Chen ,&nbsp;Yangyang Lu,&nbsp;Jialin Song,&nbsp;Shasha Wang,&nbsp;Jing Guo,&nbsp;Xiaoxi Han,&nbsp;YuanYuan Fang,&nbsp;Siyi Zhang,&nbsp;Wensheng Qiu,&nbsp;Weiwei Qi","doi":"10.1016/j.tranon.2025.102481","DOIUrl":"10.1016/j.tranon.2025.102481","url":null,"abstract":"<div><h3>Background</h3><div><strong>:</strong> Gastric cancer (GC) is a prevalent malignant tumor worldwide, with limited treatment targets. Timosaponin AIII (Tim AIII) is the naturally steroid saponin isolated from Anemarrhena, while this study initially confirms the anti-GC effect of Tim AIII.</div></div><div><h3>Methods</h3><div><strong>:</strong> MTT assay, cell cycle analysis, and wound healing assay were used to evaluate the inhibitory effects of Tim AIII on GC cells (AGS and HGC27). Evaluate the oxidative stress (OS) by measuring reactive oxygen species (ROS) and malondialdehyde (MDA), as well as the Kelch-like ECH-associated protein 1 (Keap1) - Nuclear factor erythroid-derived 2-like 2 (Nrf2) pathway. RNA sequencing and proteomics analysis were utilized to investigate deeper molecular mechanisms. To track the autophagic flux using transmission electron microscope, detecting changes in autophagy-related pathway proteins, staining with LC3B and lysosome. Experiments related to cell viability, OS, and autophagy levels were performed on normal gastric mucosal epithelial cells (GES-1) as parallel controls. Finally, Nude mouse subcutaneous tumor model to evaluate the anti-GC ability in vivo.</div></div><div><h3>Results</h3><div><strong>:</strong> Tim AIII inhibits the viability, proliferation, and migration of GC cells. Tim AIII causes OS in GC cells by the increasing intracellular ROS and MDA levels and inhibiting the Keap1-Nrf2 pathway. RNA sequencing and proteomics analysis mainly focused on the autophagy-associated pathways and lysosome in GC cells. Tim AIII activates autophagy, as indicated by an increase in the number of autophagosomes, inhibition of the PI3K-AKT pathway, and activation of the AMPK pathway in GC cells. However, Tim AIII inhibits autophagy-lysosome fusion and impairs lysosomal function, which results in autophagic flux blockage in GC cells. The Tim AIII concentration that significantly inhibited GC cells in this study was applied to GES-1 cells. The results showed that at this concentration, Tim AIII exhibited no significant cytotoxic effects on GES-1 cells, did not induce OS, and had no impact on autophagy. Finally, Tim AIII also has the ability to inhibit tumor growth in vivo.</div></div><div><h3>Significance</h3><div><strong>:</strong> In summary, the results of our study indicate Tim AIII as a novel late-stage autophagy inhibitor, which may provide novel medical possibilities for GC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"60 ","pages":"Article 102481"},"PeriodicalIF":5.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosticating salvage stereotactic radiosurgery outcomes in relapsed primary central nervous system lymphoma: A machine learning-driven decision tree analysis","authors":"Huili Zhao ,&nbsp;Shenao Zhang ,&nbsp;Lang Chen ,&nbsp;Xin Liu ,&nbsp;Aihong Cao ,&nbsp;Peng Du","doi":"10.1016/j.tranon.2025.102482","DOIUrl":"10.1016/j.tranon.2025.102482","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify key clinical risk factors affecting therapeutic outcomes in relapsed primary central nervous system lymphoma (r-PCNSL) patients undergoing stereotactic radiosurgery salvage therapy (SRS-ST) and develop a decision tree-based predictive model.</div></div><div><h3>Patients and Methods</h3><div>A retrospective analysis was performed on r-PCNSL patients undergoing SRS-ST at The Second Affiliated Hospital of Xuzhou Medical University between January 2012 and November 2021. The cohort was randomly divided into training and validation sets (7:3 ratio). The C5.0 algorithm was employed to develop a decision tree model for predicting treatment response. Model performance was evaluated using diagnostic metrics including accuracy (ACC), sensitivity, and specificity.</div></div><div><h3>Results</h3><div>A cohort of 209 patients meeting inclusion/exclusion criteria were enrolled. Survival analysis revealed a mean progression-free survival (PFS) of 7.5 ± 2.6 months and overall survival (OS) of 13.8 ± 4.1 months. Using multivariate analysis, a decision tree model was developed incorporating three critical prognostic parameters: Karnofsky Performance Status (KPS); deep brain structure involvement; and International Extranodal Lymphoma Study Group (IELSG) score. The model demonstrated robust predictive accuracy, with sensitivities of 0.880-1.000 in the training set versus 0.667-0.880 in the validation set, and corresponding specificities of 0.926-1.000 and 0.854-0.984, respectively.</div></div><div><h3>Conclusions</h3><div>Our analysis identified critical determinants of therapeutic response in r-PCNSL patients receiving SRS-ST, developing a clinically applicable decision tree model to guide hematologists and neuro-oncologists in personalizing treatment approaches.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"60 ","pages":"Article 102482"},"PeriodicalIF":5.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline mutation analysis and postoperative recurrence risk prediction in breast cancer patients from western China","authors":"Zhujun Deng ,&nbsp;Xia Xiao ,&nbsp;Biqin Mou,&nbsp;Jing Wang,&nbsp;Qiongxia Hu,&nbsp;Juan Jiang,&nbsp;Kang Xie,&nbsp;Wengeng Zhang,&nbsp;Weimin Li,&nbsp;Bojiang Chen","doi":"10.1016/j.tranon.2025.102477","DOIUrl":"10.1016/j.tranon.2025.102477","url":null,"abstract":"<div><h3>Background</h3><div>Much of our understanding of the germline mutation spectrum derives from hereditary breast cancer data in white populations. Additionally, the influence of genetic variants on breast cancer prognosis remains a topic of debate. Identifying patients at high risk of postoperative recurrence is crucial for guiding clinical decision-making; however, there is currently no reliable multigene risk prediction model tailored to the Chinese population.</div></div><div><h3>Methods</h3><div>A single-center retrospective study involving 1067 breast cancer patients was conducted. Survival analyses were performed using the Kaplan‒Meier method and Cox proportional hazards regression. Postoperative recurrence risk prediction models were developed utilizing the Cox regression methodology.</div></div><div><h3>Results</h3><div>In this cohort, 229 germline pathogenic/likely pathogenic (P/LP) mutations were identified in 215 patients (20.1 %). No significant differences in disease-free survival (DFS) were observed between germline P/LP mutation carriers and non-carriers. However, 10 single-nucleotide polymorphisms (SNPs) were significantly associated with DFS outcomes. By integrating the SNP status and clinical phenotype, a postoperative recurrence risk prediction model was established. The area under the curve values for 1- and 3-year DFS in the training set were 0.840 and 0.754. This model can accurately predict the DFS of patients in both the training set (hazard ratio [HR] 5.23, 95 % confidence interval [CI] 2.96–9.34; <em>p</em> &lt; 0.0001) and the validation set (HR 2.88, 95 % CI 1.41–6.06; <em>p</em> = 0.003)</div></div><div><h3>Conclusion</h3><div>In patients with early and locally advanced breast cancer, SNPs, rather than germline P/LP mutations, impact DFS. Using a genetic-clinical model, we successfully identified patients at high risk of postoperative recurrence.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"60 ","pages":"Article 102477"},"PeriodicalIF":5.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aptamer-mediated delivery of therapeutic oligonucleotides in glioblastoma","authors":"Giorgia Castellani ,&nbsp;Mariachiara Buccarelli ,&nbsp;Enza Cece ,&nbsp;Martina Offi ,&nbsp;Lucia Ricci-Vitiani","doi":"10.1016/j.tranon.2025.102485","DOIUrl":"10.1016/j.tranon.2025.102485","url":null,"abstract":"<div><div>Aptamers are single-stranded oligonucleotides with great versatility, acting as therapeutic molecules with anticancer properties but also as delivery systems. A growing number of studies showed that aptamers can be properly designed to recognize a specific target, to conjugate drugs, nanoparticles or nucleic acid therapeutics (NATs) and to cross the blood brain barrier. In this review, we summarized the main advantages of aptamers as delivery system, focusing our attention on aptamer-mediated delivery of therapeutic oligonucleotides in glioblastoma. Glioblastoma represents the most common and aggressive primary malignant brain tumor in adults, with a median survival ranging from 14.6 to 20.5 months. Currently, the standard treatment of newly diagnosed tumor includes surgical resection followed by radiotherapy and chemotherapy with the alkylating agent temozolomide. However, the overall efficacy is limited and most patients relapse within a few months, calling attention on the development of alternative therapeutic strategies. Particularly, we discussed research studies on NAT delivery mediated by aptamer chimeras and aptamer-nanoparticle complexes able to impair various processes involved in glioblastoma tumorigenesis. This overview will help to highlight how aptamers, thanks to their advantages, could represent a promising tool for the development of innovative therapeutic approaches for glioblastoma treatment.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"60 ","pages":"Article 102485"},"PeriodicalIF":5.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}