NPJ Precision Oncology最新文献_第7页

MDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-03 DOI: 10.1038/s41698-025-00823-x

Vishesh Khanna, Gohar Eslami, Rochelle Reyes, Robert Diep, Sebastian Fernandez-Pol, Henning Stehr, Carlos Jose Suarez, Harlan Pinto, James M Ford, Tian Yi Zhang, Christopher T Chen

{"title":"MDM2 inhibition is associated with the emergence of TP53-altered clonal hematopoiesis.","authors":"Vishesh Khanna, Gohar Eslami, Rochelle Reyes, Robert Diep, Sebastian Fernandez-Pol, Henning Stehr, Carlos Jose Suarez, Harlan Pinto, James M Ford, Tian Yi Zhang, Christopher T Chen","doi":"10.1038/s41698-025-00823-x","DOIUrl":"10.1038/s41698-025-00823-x","url":null,"abstract":"Murine double minute 2 (MDM2) inhibitors have shown promising activity in TP53-wild type tumors and are under active investigation across a spectrum of malignancies. Herein, we report a 51-year-old female with MDM2-amplified, TP53-wild type adenoid cystic carcinoma who was treated with a MDM2 inhibitor and developed persistent pancytopenia despite drug discontinuation. Her pancytopenia was associated with 20 distinct pathogenic TP53 mutations in peripheral blood and bone marrow not present in drug-resistant tumor tissue. Plasma TP53 mutations were similarly detected among 4 other patients treated at our institution, with the number of mutations correlating strongly with duration of treatment. This case suggests that MDM2 inhibitors are associated with TP53 clonal hematopoiesis, which may confer a risk of subsequent myeloid malignancy. As multiple MDM2 inhibitor trials are ongoing, our findings underscore the need for further investigation into the potential long-term deleterious effects of these inhibitors in the hematopoietic stem and progenitor compartment.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"34"},"PeriodicalIF":6.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123275","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

Annotation-free deep learning for predicting gene mutations from whole slide images of acute myeloid leukemia.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-02-03 DOI: 10.1038/s41698-025-00804-0

Bo-Han Wei, Xavier Cheng-Hong Tsai, Kuo-Jui Sun, Min-Yen Lo, Sheng-Yu Hung, Wen-Chien Chou, Hwei-Fang Tien, Hsin-An Hou, Chien-Yu Chen

{"title":"Annotation-free deep learning for predicting gene mutations from whole slide images of acute myeloid leukemia.","authors":"Bo-Han Wei, Xavier Cheng-Hong Tsai, Kuo-Jui Sun, Min-Yen Lo, Sheng-Yu Hung, Wen-Chien Chou, Hwei-Fang Tien, Hsin-An Hou, Chien-Yu Chen","doi":"10.1038/s41698-025-00804-0","DOIUrl":"10.1038/s41698-025-00804-0","url":null,"abstract":"The rapid development of deep learning has revolutionized medical image processing, including analyzing whole slide images (WSIs). Despite the demonstrated potential for characterizing gene mutations directly from WSIs in certain cancers, challenges remain due to image resolution and reliance on manual annotations for acute myeloid leukemia (AML). We, therefore, propose a deep learning model based on multiple instance learning (MIL) with ensemble techniques to predict gene mutations from AML WSIs. Our model predicts NPM1 mutations and FLT3-ITD without requiring patch-level or cell-level annotations. Using a dataset of 572 WSIs, the largest database with both WSI and genetic mutation information, our model achieved an AUC of 0.90 ± 0.08 for NPM1 and 0.80 ± 0.10 for FLT3-ITD in the testing cohort. Additionally, we found that blasts are pivotal indicators for gene mutation predictions, with their proportions varying between mutated and standard WSIs, highlighting the clinical potential of AML WSI analysis.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"35"},"PeriodicalIF":6.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123274","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

The burden and temporal trend of early onset pancreatic cancer based on the GBD 2021.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-01-30 DOI: 10.1038/s41698-025-00820-0

Zongbiao Tan, Yang Meng, Yanrui Wu, Junhai Zhen, Haodong He, Yu Pu, Jixiang Zhang, Weiguo Dong

引用次数: 0

A comprehensive evaluation of histopathology foundation models for ovarian cancer subtype classification.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-01-30 DOI: 10.1038/s41698-025-00799-8

Jack Breen, Katie Allen, Kieran Zucker, Lucy Godson, Nicolas M Orsi, Nishant Ravikumar

{"title":"A comprehensive evaluation of histopathology foundation models for ovarian cancer subtype classification.","authors":"Jack Breen, Katie Allen, Kieran Zucker, Lucy Godson, Nicolas M Orsi, Nishant Ravikumar","doi":"10.1038/s41698-025-00799-8","DOIUrl":"10.1038/s41698-025-00799-8","url":null,"abstract":"Histopathology foundation models show great promise across many tasks, but analyses have been limited by arbitrary hyperparameters. We report the most rigorous single-task validation study to date, specifically in the context of ovarian carcinoma morphological subtyping. Attention-based multiple instance learning classifiers were compared using three ImageNet-pretrained encoders and fourteen foundation models, each trained with 1864 whole slide images and validated through hold-out testing and two external validations (the Transcanadian Study and OCEAN Challenge). The best-performing classifier used the H-optimus-0 foundation model, with balanced accuracies of 89%, 97%, and 74%, though UNI achieved similar results at a quarter of the computational cost. Hyperparameter tuning the classifiers improved performance by a median 1.9% balanced accuracy, with many improvements being statistically significant. Foundation models improve classification performance and may allow for clinical utility, with models providing a second opinion in challenging cases and potentially improving the accuracy and efficiency of diagnoses.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"33"},"PeriodicalIF":6.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067036","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

Progress in personalized immunotherapy for patients with brain metastasis.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-01-29 DOI: 10.1038/s41698-025-00812-0

Lalit Patel, Nikola Kolundzic, Malak Abedalthagafi

引用次数: 0

Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-01-29 DOI: 10.1038/s41698-025-00817-9

Muthana Al Abo, Wen-Chi Foo, Lauren E Howard, Shannon McGue, Bonnie Lacroix, Julie Kephart, Angela Clayton, Blair Thornburg, Monika Anand, Michael B Rothberg, Shannon J McCall, Jiaoti Huang, Thomas A Esther, Judd W Moul, Michael N Ferrandino, Thomas J Polascik, Cary N Robertson, Brant A Inman, Andrew J Armstrong, Yuan Wu, Terry Hyslop, Daniel J George, Steven R Patierno, Jennifer A Freedman

{"title":"Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence.","authors":"Muthana Al Abo, Wen-Chi Foo, Lauren E Howard, Shannon McGue, Bonnie Lacroix, Julie Kephart, Angela Clayton, Blair Thornburg, Monika Anand, Michael B Rothberg, Shannon J McCall, Jiaoti Huang, Thomas A Esther, Judd W Moul, Michael N Ferrandino, Thomas J Polascik, Cary N Robertson, Brant A Inman, Andrew J Armstrong, Yuan Wu, Terry Hyslop, Daniel J George, Steven R Patierno, Jennifer A Freedman","doi":"10.1038/s41698-025-00817-9","DOIUrl":"10.1038/s41698-025-00817-9","url":null,"abstract":"Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry. Clinical follow-up revealed increased biochemical recurrence (BCR) among Black patients compared to White patients with high-grade PCa. Transcriptomic analysis identified differential alternative RNA splicing events (ARSs) between Black and White PCa patients. Genes undergoing genetic ancestry-concordant ARSs in high-grade or low-grade tumors involved cancer promoting genes. Most genes undergoing genetic ancestry-concordant ARSs did not exhibit differential aggregate gene expression or alternative polyadenylation. A number of the genetic ancestry-concordant ARSs associated with BCR; thus, genetic ancestry-concordant RNA splice variants may represent unique targets for PCa precision oncology.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"30"},"PeriodicalIF":6.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067050","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

A morphometric signature to identify ductal carcinoma in situ with a low risk of progression.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-01-28 DOI: 10.1038/s41698-024-00769-6

Marcelo Sobral-Leite, Simon P Castillo, Shiva Vonk, Hendrik A Messal, Xenia Melillo, Noomie Lam, Brandi de Bruijn, Yeman B Hagos, Myrna van den Bos, Joyce Sanders, Mathilde Almekinders, Lindy L Visser, Emma J Groen, Petra Kristel, Caner Ercan, Leyla Azarang, Jacco van Rheenen, E Shelley Hwang, Yinyin Yuan, Renee Menezes, Esther H Lips, Jelle Wesseling

{"title":"A morphometric signature to identify ductal carcinoma in situ with a low risk of progression.","authors":"Marcelo Sobral-Leite, Simon P Castillo, Shiva Vonk, Hendrik A Messal, Xenia Melillo, Noomie Lam, Brandi de Bruijn, Yeman B Hagos, Myrna van den Bos, Joyce Sanders, Mathilde Almekinders, Lindy L Visser, Emma J Groen, Petra Kristel, Caner Ercan, Leyla Azarang, Jacco van Rheenen, E Shelley Hwang, Yinyin Yuan, Renee Menezes, Esther H Lips, Jelle Wesseling","doi":"10.1038/s41698-024-00769-6","DOIUrl":"10.1038/s41698-024-00769-6","url":null,"abstract":"Ductal carcinoma in situ (DCIS) may progress to ipsilateral invasive breast cancer (iIBC), but often never will. Because DCIS is treated as early breast cancer, many women with harmless DCIS face overtreatment. To identify features associated with progression, we developed an artificial intelligence-based DCIS morphometric analysis pipeline (AIDmap) on hematoxylin-eosin-stained (H&E) tissue sections. We analyzed 689 digitized H&Es of pure primary DCIS of which 226 were diagnosed with subsequent iIBC and 463 were not. The distribution of 15 duct morphological measurements was summarized in 55 morphometric variables. A ridge regression classifier with cross validation predicted 5-years-free of iIBC with an area-under the curve of 0.67 (95% CI 0.57-0.77). A combined clinical-morphometric signature, characterized by small-sized ducts, a low number of cells and a low DCIS/stroma ratio, was associated with outcome (HR = 0.56; 95% CI 0.28-0.78). AIDmap has potential to identify harmless DCIS that may not need treatment.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"25"},"PeriodicalIF":6.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059126","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

Naltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotype.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-01-28 DOI: 10.1038/s41698-025-00815-x

Viviane Nascimento Da Conceicao, Yuyang Sun, Manigandan Venkatesan, Jorge De La Chapa, Karthik Ramachandran, Rahul S Jasrotia, Victor Drel, Xiufang Chai, Bibhuti B Mishra, Muniswamy Madesh, Brij B Singh

{"title":"Naltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotype.","authors":"Viviane Nascimento Da Conceicao, Yuyang Sun, Manigandan Venkatesan, Jorge De La Chapa, Karthik Ramachandran, Rahul S Jasrotia, Victor Drel, Xiufang Chai, Bibhuti B Mishra, Muniswamy Madesh, Brij B Singh","doi":"10.1038/s41698-025-00815-x","DOIUrl":"10.1038/s41698-025-00815-x","url":null,"abstract":"Macrophage plasticity is critical for maintaining immune function and developing solid tumors; however, the macrophage polarization mechanism remains incompletely understood. Our findings reveal that Mg2+ entry through distinct plasma membrane channels is critical to macrophage plasticity. Naïve macrophages displayed a previously unidentified Mg2+ dependent current, and TRPM7-like activity, which modulates its survival. Significantly, in M1 macrophages, Mg2+ entry is facilitated by a novel Mg²-dependent current that relies on extracellular Mg2+, which was crucial for activating iNOS/NFκB pathways and cellular bioenergetics, which drives pro-inflammatory cytokines. Conversely, in M2 macrophages, Mg2+ entry occurs primarily through TRPM7 channels, pivotal for IL-4 and IL-10-mediated anti-inflammatory cytokine secretion. Notably, the Mg2+ deficient diet or addition of TRPM7 agonist Naltriben suppresses the M1 phenotype while promoting angiogenic factors and fostering tumor growth. These findings suggest that Mg2+ flux via specific channels is indispensable for macrophage polarization, with its dysregulation playing a pivotal role in tumor progression.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"29"},"PeriodicalIF":6.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059387","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

A prospective pragmatic evaluation of automatic trial matching tools in a molecular tumor board.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-01-27 DOI: 10.1038/s41698-025-00806-y

Lilia Gueguen, Louise Olgiati, Clément Brutti-Mairesse, Alric Sans, Vincent Le Texier, Loic Verlingue

引用次数: 0

Histopathology and proteomics are synergistic for high-grade serous ovarian cancer platinum response prediction.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-01-26 DOI: 10.1038/s41698-025-00808-w

Oz Kilim, Alex Olar, András Biricz, Lilla Madaras, Péter Pollner, Zoltán Szállási, Zsofia Sztupinszki, István Csabai

{"title":"Histopathology and proteomics are synergistic for high-grade serous ovarian cancer platinum response prediction.","authors":"Oz Kilim, Alex Olar, András Biricz, Lilla Madaras, Péter Pollner, Zoltán Szállási, Zsofia Sztupinszki, István Csabai","doi":"10.1038/s41698-025-00808-w","DOIUrl":"10.1038/s41698-025-00808-w","url":null,"abstract":"Patients with High-Grade Serous Ovarian Cancer (HGSOC) exhibit varied responses to treatment, with 20-30% showing de novo resistance to platinum-based chemotherapy. While hematoxylin-eosin (H&E)-stained pathological slides are used for routine diagnosis of cancer type, they may also contain diagnostically useful information about treatment response. Our study demonstrates that combining H&E-stained whole slide images (WSIs) with proteomic signatures using a multimodal deep learning framework significantly improves the prediction of platinum response in both discovery and validation cohorts. This method outperforms the Homologous Recombination Deficiency (HRD) score in predicting platinum response and overall patient survival. Our study suggests that histology and proteomics contain complementary information about biological processes determining response to first line platinum treatment in HGSOC. This integrative approach has the potential to improve personalized treatment and provide insights into the therapeutic vulnerabilities of HGSOC.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"27"},"PeriodicalIF":6.8,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040058","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