NPJ Precision Oncology最新文献_第2页

HDAC6 facilitates LUAD progression by inducing EMT and enhancing macrophage polarization towards the M2 phenotype. HDAC6通过诱导EMT和增强巨噬细胞向M2表型的极化来促进LUAD的进展。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-05-22 DOI: 10.1038/s41698-025-00949-y

Yantao Jiang, Ju Zhang, Junjie Yu, Wei Luo, Qingwu Du, Wenting Liu, Qi Xu, Xueyang Li, Huiyan Liu, Dingzhi Huang, Tingting Qin

引用次数: 0

Tumor diagnosis recharacterization enabled by comprehensive genomic profiling to guide precision medicine strategy. 肿瘤诊断再表征，使全面基因组分析指导精准医疗策略。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-05-21 DOI: 10.1038/s41698-025-00942-5

Ann Carr, Jennifer B Jackson, Chris Coldren, Pranil Chandra, Faezeh Koohestani, Michelle Shiller, Robert Auber

{"title":"Tumor diagnosis recharacterization enabled by comprehensive genomic profiling to guide precision medicine strategy.","authors":"Ann Carr, Jennifer B Jackson, Chris Coldren, Pranil Chandra, Faezeh Koohestani, Michelle Shiller, Robert Auber","doi":"10.1038/s41698-025-00942-5","DOIUrl":"10.1038/s41698-025-00942-5","url":null,"abstract":"Comprehensive genomic profiling (CGP) via next-generation sequencing is standard clinical practice for advanced and metastatic cancers in the U.S. and can help identify clinically actionable alterations in patients who may benefit from targeted therapies. CGP can also complement clinicopathological findings and in certain cases, may lead to diagnostic recharacterization resulting in more precise therapeutic strategies. Here, we highlight examples where molecular findings resulted in tumor re-evaluation and subsequent recharacterization. Twenty-eight cases where CGP results were inconsistent with initial pathological diagnosis and clinical presentation were selected for secondary clinicopathological review to explore alternative diagnostic explanations more consistent with the genomic results. Genomic profiling identified clinically actionable and prognostic variants leading to more accurate therapeutic recommendations based on the updated diagnoses highlighting the value of CGP beyond biomarker detection for therapy selection and supporting its complementary use in diagnostic confirmation to unveil opportunities for precision medicine strategies.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"149"},"PeriodicalIF":6.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An artificial intelligence-based model for prediction of clonal hematopoiesis variants in cell-free DNA samples. 基于人工智能的无细胞DNA样本克隆造血变异预测模型。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-05-20 DOI: 10.1038/s41698-025-00921-w

Gustavo Arango-Argoty, Marzieh Haghighi, Gerald J Sun, Elizabeth Y Choe, Aleksandra Markovets, J Carl Barrett, Zhongwu Lai, Etai Jacob

引用次数: 0

Multimodal spatial proteomic profiling in acute myeloid leukemia. 急性髓系白血病的多模态空间蛋白质组学分析。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-05-20 DOI: 10.1038/s41698-025-00897-7

Christopher P Ly, Ivo Veletic, Christopher D Pacheco, Enes Dasdemir, Fatima Z Jelloul, Sammy Ferri-Borgogno, Akshay V Basi, Javier A Gomez, Jessica L Root, Patrick K Reville, Sonali Jindal, Sreyashi Basu, Padmanee Sharma, Andres E Quesada, Carlos Bueso-Ramos, Taghi Manshouri, Branko Cuglievan, Miriam Garcia, Jared K Burks, Hussein A Abbas

{"title":"Multimodal spatial proteomic profiling in acute myeloid leukemia.","authors":"Christopher P Ly, Ivo Veletic, Christopher D Pacheco, Enes Dasdemir, Fatima Z Jelloul, Sammy Ferri-Borgogno, Akshay V Basi, Javier A Gomez, Jessica L Root, Patrick K Reville, Sonali Jindal, Sreyashi Basu, Padmanee Sharma, Andres E Quesada, Carlos Bueso-Ramos, Taghi Manshouri, Branko Cuglievan, Miriam Garcia, Jared K Burks, Hussein A Abbas","doi":"10.1038/s41698-025-00897-7","DOIUrl":"10.1038/s41698-025-00897-7","url":null,"abstract":"Acute myeloid leukemia (AML) resides in an immune-rich microenvironment, yet, immune-based therapies have faltered in eliciting durable responses. Bridging this paradox requires a comprehensive understanding of leukemic interactions within the bone marrow microenvironment. We optimized a high-throughput tissue-microarray-based pipeline for high-plex spatial immunofluorescence and mass cytometry imaging on a single slide, capturing immune, tumor, and structural components. Using unbiased clustering on the spatial K function, we unveiled the presence of tertiary lymphoid-like aggregates in bone marrow, which we validated using spatial transcriptomics and an independent proteomics approach. We then found validated TLS signatures predictive of outcomes in AML using an integrated public 480-patient transcriptomic dataset. By harnessing high-plex spatial proteomics, we open the possibility of discovering novel structures and interactions that underpin leukemic immune response. Further, our study's methodologies and resources can be adapted for other bone marrow diseases where decalcification and autofluorescence present challenges.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"148"},"PeriodicalIF":6.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging innovations in theranostics for pancreatic neuroendocrine tumors. 胰腺神经内分泌肿瘤治疗的新进展。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-05-19 DOI: 10.1038/s41698-025-00938-1

Anita Karimi, Christina Bogdani, Elisabeth O'Dwyer, Despina Siolas

引用次数: 0

Comparative analysis of RNA expression identifies effective targeted drug in myoepithelial carcinoma. RNA表达对比分析确定肌上皮癌有效靶向药物。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-05-17 DOI: 10.1038/s41698-025-00918-5

Yvonne A Vasquez, Lauren Sanders, Holly C Beale, A Geoffrey Lyle, Ellen T Kephart, Katrina Learned, Jennifer Peralez, Amy Li, Min Huang, Kimberly A Pyke-Grimm, Serena Y Tan, Sofie R Salama, David Haussler, Isabel Bjork, Olena M Vaske, Sheri L Spunt

{"title":"Comparative analysis of RNA expression identifies effective targeted drug in myoepithelial carcinoma.","authors":"Yvonne A Vasquez, Lauren Sanders, Holly C Beale, A Geoffrey Lyle, Ellen T Kephart, Katrina Learned, Jennifer Peralez, Amy Li, Min Huang, Kimberly A Pyke-Grimm, Serena Y Tan, Sofie R Salama, David Haussler, Isabel Bjork, Olena M Vaske, Sheri L Spunt","doi":"10.1038/s41698-025-00918-5","DOIUrl":"10.1038/s41698-025-00918-5","url":null,"abstract":"Myoepithelial carcinoma is an ultra-rare pediatric solid tumor with no targeted treatments. Clinical implementation of tumor RNA sequencing (RNA-Seq) for identifying therapeutic targets is underexplored in pediatric cancer. We previously published the Comparative Analysis of RNA Expression (CARE), a framework for incorporating RNA-Seq-derived gene expression into the clinic for difficult-to-treat pediatric cancers. Here, we discuss a 4-year-old male diagnosed with myoepithelial carcinoma who was treated at Stanford Medicine Children's Health. A metastatic lung nodule from the patient underwent standard-of-care tumor DNA profiling and CARE analysis, wherein the patient's tumor RNA-Seq profile was compared to over 11,000 uniformly analyzed tumor profiles from public data repositories. DNA profiling yielded no actionable mutations. CARE identified overexpression biomarkers and nominated a treatment that produced a durable clinical response. These findings underscore the utility of data sharing and concurrent analysis of large genomic datasets for clinical benefit, particularly for rare cancers with unknown biological drivers.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"145"},"PeriodicalIF":6.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hepatocellular carcinoma cells downregulate PGAM2 via SIRT2-mediated deacetylation modification to enhance aerobic glycolysis. 肝癌细胞通过sirt2介导的去乙酰化修饰下调PGAM2以增强有氧糖酵解。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-05-16 DOI: 10.1038/s41698-025-00930-9

Zexuan Wang, Yaoyu Guo, Kefei Hu, Tingjiang He, Tong Qin, Ludan Zhang, Fang Xu, Yuanzhi Xu, Mingjiao Cheng, Jintao Zhang, Qianwei Zhao

{"title":"Hepatocellular carcinoma cells downregulate PGAM2 via SIRT2-mediated deacetylation modification to enhance aerobic glycolysis.","authors":"Zexuan Wang, Yaoyu Guo, Kefei Hu, Tingjiang He, Tong Qin, Ludan Zhang, Fang Xu, Yuanzhi Xu, Mingjiao Cheng, Jintao Zhang, Qianwei Zhao","doi":"10.1038/s41698-025-00930-9","DOIUrl":"10.1038/s41698-025-00930-9","url":null,"abstract":"Phosphoglycerate mutase 2 (PGAM2) is a crucial glycolytic enzyme. Recently, we have found that both the protein and acetylation levels of PGAM2 are down-regulated in hepatocellular carcinoma (HCC) tissues. However, the functional significance of PGAM2 in HCC progression remains poorly characterized. In this study, we demonstrated that PGAM2 functioned as a tumor suppressor in HCC progression, and knockdown of PGAM2 promoted proliferation of HCC cells and tumor growth both in vitro and in vivo. Moreover, we identified lysine 100 (K100) in PGAM2 as the predominant deacetylation site of sirtuin-2 (SIRT2), and that deacetylation of K100 destabilized PGAM2 by promoting its ubiquitination and degradation. Importantly, we discovered that PGAM2 suppressed aerobic glycolysis through an enzymatic activity-independent mechanism in HCC cells. Mechanistic investigations revealed that PGAM2 knockdown upregulated lactate dehydrogenase A (LDHA) expression via activation of the signal transducer and activator of transcription 3 (STAT3). Furthermore, we found that knockdown of PGAM2 sensitized HCC cells to sorafenib treatment. In conclusion, these findings elucidate the tumor-suppressive role of PGAM2 in HCC progression and its post-translational regulation through SIRT2-mediated deacetylation, which provide novel biomarkers and therapeutic targets for HCC treatment.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"143"},"PeriodicalIF":6.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate. 以硫酸癌胎软骨素为靶点检测循环肿瘤细胞中的多种肿瘤。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-05-16 DOI: 10.1038/s41698-025-00936-3

Caroline Løppke, Randi Ugleholdt, Christine F Secher, Nicolai T Sand, Joana Mujollari, Tobias Gustavsson, Robert Dagil, Thor G Theander, Ali Salanti, Kristoffer S Rohrberg, Mette Ø Agerbæk

{"title":"Multi-cancer detection of circulating tumor cells by targeting oncofetal chondroitin sulfate.","authors":"Caroline Løppke, Randi Ugleholdt, Christine F Secher, Nicolai T Sand, Joana Mujollari, Tobias Gustavsson, Robert Dagil, Thor G Theander, Ali Salanti, Kristoffer S Rohrberg, Mette Ø Agerbæk","doi":"10.1038/s41698-025-00936-3","DOIUrl":"10.1038/s41698-025-00936-3","url":null,"abstract":"Liquid biopsies for the detection of circulating tumor cells (CTCs) are a promising strategy for personalized cancer management. However, traditional CTC detection platforms are often constrained to epithelial cancers, vulnerable to phenotypic changes, and rely on specialized devices for standardized detection, restricting the clinical utility across diverse cancer types and healthcare settings. In this study, we present a tumor-agnostic, platform-independent CTC detection strategy based on recognition of the cancer-specific glycosylation, oncofetal chondroitin sulfate (ofCS). Through coupling of the ofCS-binding protein, VAR2CSA, to a fluorophore-carrying dextran polymer, we successfully detected ofCS-positive CTCs from blood samples in two diverse and independent cohorts comprising early- and late-stage cancer patients of both epithelial and non-epithelial tumor origin. In addition, no ofCS-positive cells were detected in non-malignant controls. Thus, targeting of ofCS has the potential to expand the range of patients who could benefit from CTC analysis, enhancing the clinical utility in various cancer settings.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"144"},"PeriodicalIF":6.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Benchmarking large language models GPT-4o, llama 3.1, and qwen 2.5 for cancer genetic variant classification. 对大型语言模型gpt - 40、llama 3.1和qwen 2.5进行癌症遗传变异分类的基准测试。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-05-15 DOI: 10.1038/s41698-025-00935-4

Kuan-Hsun Lin, Tzu-Hang Kao, Lei-Chi Wang, Chen-Tsung Kuo, Paul Chih-Hsueh Chen, Yuan-Chia Chu, Yi-Chen Yeh

{"title":"Benchmarking large language models GPT-4o, llama 3.1, and qwen 2.5 for cancer genetic variant classification.","authors":"Kuan-Hsun Lin, Tzu-Hang Kao, Lei-Chi Wang, Chen-Tsung Kuo, Paul Chih-Hsueh Chen, Yuan-Chia Chu, Yi-Chen Yeh","doi":"10.1038/s41698-025-00935-4","DOIUrl":"https://doi.org/10.1038/s41698-025-00935-4","url":null,"abstract":"Classifying cancer genetic variants based on clinical actionability is crucial yet challenging in precision oncology. Large language models (LLMs) offer potential solutions, but their performance remains underexplored. This study evaluates GPT-4o, Llama 3.1, and Qwen 2.5 in classifying genetic variants from the OncoKB and CIViC databases, as well as a real-world dataset derived from FoundationOne CDx reports. GPT-4o achieved the highest accuracy (0.7318) in distinguishing clinically relevant variants from variants of unknown clinical significance (VUS), outperforming Qwen 2.5 (0.5731) and Llama 3.1 (0.4976). LLMs demonstrated better concordance with expert annotations for variants with strong clinical evidence but exhibited greater inconsistencies for those with weaker evidence. All three models showed a tendency to assign variants to higher evidence levels, suggesting a propensity for overclassification. Prompt engineering significantly improved accuracy, while retrieval-augmented generation (RAG) further enhanced performance. Stability analysis across 100 iterations revealed greater consistency with the CIViC system than with OncoKB. These findings highlight the promise of LLMs in cancer genetic variant classification while underscoring the need for further optimization to improve accuracy, consistency, and clinical applicability.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"141"},"PeriodicalIF":6.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unlocking the potential of TIGIT in enhancing therapeutic strategies for acute myeloid leukemia through combined azacitidine therapy. 释放TIGIT的潜力，通过联合阿扎胞苷治疗增强急性髓系白血病的治疗策略。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-05-15 DOI: 10.1038/s41698-025-00933-6

Yv-Yin Zhang, Jia-Jun He, Yi-Lin Liu, Ruo-Nan Shao, Kun-Hao Bai, Xue-Ping Li, Tao Guo, Pei-Hong Wang, Yu-Jun Dai

{"title":"Unlocking the potential of TIGIT in enhancing therapeutic strategies for acute myeloid leukemia through combined azacitidine therapy.","authors":"Yv-Yin Zhang, Jia-Jun He, Yi-Lin Liu, Ruo-Nan Shao, Kun-Hao Bai, Xue-Ping Li, Tao Guo, Pei-Hong Wang, Yu-Jun Dai","doi":"10.1038/s41698-025-00933-6","DOIUrl":"10.1038/s41698-025-00933-6","url":null,"abstract":"Immune checkpoint blockade (ICB) therapy has emerged as a pivotal advancement in cancer treatment, yet its efficacy varies among patients and resistance can develop. This study focuses on TIGIT, a newly identified immune checkpoint, to explore its expression, prognostic significance, and therapeutic potential in hematologic malignancies, particularly acute myeloid leukemia (AML). In this study, we found TIGIT highest expression levels in bone marrow and lymphoid tissues, with enrichment in immune cells such as NK-T cells and regulatory T cells (Tregs). A prognostic model incorporating TIGIT expression and other immune-related genes effectively stratified AML patients into high-risk and low-risk groups, with the former displaying significantly shorter overall survival times. Our model outperformed traditional prognostic factors, highlighting TIGIT's potential as a superior predictive biomarker. Additionally, our in vitro and in vivo studies showed that combining tiragolumab with azacitidine (AZA) synergistically enhanced anti-tumor efficacy, reducing tumor burden and extending survival in a murine AML model. Our findings underscore TIGIT's role in hematologic malignancies and its potential as a therapeutic target in AML. The combination of AZA with TIGIT inhibition offers a promising new approach for AML treatment, warranting further clinical evaluation.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"142"},"PeriodicalIF":6.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0