NPJ Precision Oncology最新文献

{"title":"Integrating genomic and pathological characteristics to enhance prognostic precision in advanced NSCLC.","authors":"Yingjie Han, Junxun Ma, Zhefeng Liu, Lijie Wang, Fan Zhang, Di Huang, Siyao Liu, Jifang Hu, Wenhua Xiao, Hong Wang, Juyi Wen, Haifeng Qin, Hongjun Gao, Xiaosong Li, Ziwei Huang, Jiali Zhang, Yue Zhang, Dawei Sun, Junyan Su, Jing Chen, Beifang Niu, Haitao Tao, Bo Yang, Xiaoqing Liu, Jinliang Wang, Yi Hu","doi":"10.1038/s41698-025-01056-8","DOIUrl":"https://doi.org/10.1038/s41698-025-01056-8","url":null,"abstract":"<p><p>Although immunotherapy combined with chemotherapy (ICT) is the standard treatment for advanced non-small cell lung cancer (NSCLC), identification of reliable prognostic biomarkers remains challenging. In this multicenter study, we performed next-generation sequencing of tumor samples from 162 patients receiving first-line ICT at the Chinese PLA General Hospital and collected their pathological image information. First, we established a model to predict the risk of tumor progression based on genomic characteristics. Furthermore, a deep learning method was employed to recognize different cell types from pathological images, which significantly improved the accuracy of progression-free survival (PFS) and overall survival (OS) prediction. In summary, we constructed a Prognostic Multimodal Classifier for Progression (PMCP) that possesses the capability to precisely forecast PFS and OS. Patients with the PMCP1 subtype exhibit a low risk of progression and demonstrate a higher proportion of epithelial cells. PMCP highlighted the potential value of multimodal biomarkers in guiding clinical decisions regarding ICT. The area under curve (AUC) for predicting PFS was 0.807. This study revealed the importance of integrating genomic and pathological data to improve prognostic accuracy and enable personalized treatment for patients with advanced NSCLC.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"271"},"PeriodicalIF":6.8,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of HMGA1 on tumorigenesis, prognosis and immune microenvironment in HNSCC: a multi-omics study.","authors":"Ziang Xu, Moxu Wang, Jilin Cai, Tianxiao Wang, Nan Ni, Tao Liu, Maojie Xue, Xiang Wang, Zhixuan Liu, Hua Yuan, Wei Zhang, Ruyang Zhang","doi":"10.1038/s41698-025-01068-4","DOIUrl":"https://doi.org/10.1038/s41698-025-01068-4","url":null,"abstract":"<p><p>HMGA1 plays an important role in a variety of biological processes. However, it is still unclear what role HMGA1 plays in HNSCC. By integrating multi-omics data from public and private cohorts, we conducted a comprehensive analysis. The results showed that HMGA1 expression was significantly higher in HNSCC tumor tissue, correlated with poor prognosis. Increased HMGA1 expression indicated distinct somatic mutations and heavier tumor mutation burden, meanwhile, had significant interaction with several immune checkpoints. Single-cell analysis suggested that HMGA1 was highly enriched in malignant cells. In-vitro and in-vivo experiments also suggested that HMGA1 promoted the proliferation, migration and activation of HNSCC cells. Upstream analysis showed that cg25207224_HMGA1 tested by oral rinse specimen maybe a non-invasive in-vitro predictive marker for prognostic prediction of HNSCC. Our study revealed the impact of HMGA1 on tumorigenesis, prognosis and immune microenvironment in HNSCC from a multi-omics perspective and provided a therapeutic target for HNSCC patients.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"269"},"PeriodicalIF":6.8,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal tumor microenvironment signature of colorectal cancer for prediction prognosis and chemotherapy benefit.","authors":"Wei Jiang, Kun Yang, Chanchan Xiao, Hongli Ji, Botao Yan, Shuhan Zhao, Biao Zhang, Jiaxin Cheng, Shuoyu Xu, Guangxing Wang, Zexi Lin, Jianping Lu, Gang Chen, Shuangmu Zhuo, Jun Yan","doi":"10.1038/s41698-025-01069-3","DOIUrl":"https://doi.org/10.1038/s41698-025-01069-3","url":null,"abstract":"<p><p>The current tumor‒node‒metastasis (TNM) staging system cannot provide sufficient information for prognosis and chemotherapy benefits in patients with colorectal cancer (CRC). The tumor microenvironment plays a critical role in disease progression and therapeutic response. Here, we developed and validated a multimodal tumor microenvironment signature of CRC (MTMS_CRC) using 1314 CRC patients to enhance prognosis and chemotherapy benefit predictions. We found that the MTMS_CRC is an independent predictor of prognosis. Furthermore, incorporating the MTMS_CRC and clinicopathological characteristics into the integrated nomograms significantly outperformed traditional models and the TNM staging system. Shapley values identified the MTMS_CRC as the most important predictor. Moreover, chemotherapy had no impact on prognosis in nomogram-predicted low-risk score patients but was associated with improved prognosis in medium and high-risk score patients. In summary, the MTMS_CRC is a valuable prognostic predictor in CRC patients and the integrated nomogram may help identify those who could benefit from chemotherapy.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"270"},"PeriodicalIF":6.8,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative bioinformatics analysis and experimental validation identify CHEK1 as an unfavorable prognostic biomarker related to immunosuppressive phenotypes in soft tissue sarcomas.","authors":"Chao Rong, Yun Liu, Fang Xiang, Xin Zhao, Jinjin Zhang, Zuorun Xiao, Jinsha Wang, Lin Chen, Zhiqi Guo, Ziyu Zhang, Jingnan An, Jing Shen, Jochen Hess, Xiaodong Yuan, Qiong Zhang, Shouli Wang","doi":"10.1038/s41698-025-01064-8","DOIUrl":"https://doi.org/10.1038/s41698-025-01064-8","url":null,"abstract":"<p><p>Soft tissue sarcomas (STS), including rhabdomyosarcoma (RMS), exhibit significant heterogeneity and limited responsiveness to immune checkpoint blockade (ICB). Unsupervised tumor immune phenotype based on multi-omics expression profiling of STS has been less studied. To reveal the tumor immune phenotype of STS and identify promising therapeutic targets, multi-omics expression profiling across various subtypes of STS was investigated. Here, we established a novel molecular classifier based on immune cell subsets related to TGFβ1 and IFNγ to identify distinct immune phenotypes with higher or lower cytotoxic contents. Immune-high clusters demonstrated enriched immune cell infiltration, elevated IFNγ-related signatures, and favorable clinical outcomes. In contrast, immune-low clusters were enriched for immunosuppressive cell types and exhibited poor survival. CHEK1 emerged as a key node associated with immunosuppressive phenotypes and was significantly overexpressed in immune-low tumors. In situ analysis of independent validation cohorts revealed the significant correlation between CHEK1 and tumor-infiltrating immune cells. Collectively, our findings establish a novel risk assessment strategy for RMS and STS patients, and highlight the potential of CHEK1 as a promising therapeutic target in combination with immune checkpoint inhibitor therapy.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"268"},"PeriodicalIF":6.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of breast cancer subtypes and drug response prediction through forward and reverse translation.","authors":"Julie Karam, Paul A Rejto, Jadwiga Renata Bienkowska, Xinmeng Jasmine Mu, Whijae Roh","doi":"10.1038/s41698-025-01062-w","DOIUrl":"10.1038/s41698-025-01062-w","url":null,"abstract":"<p><p>Breast cancer (BRCA) is the most frequently diagnosed cancer among women and the second leading cause of cancer-related mortality worldwide. Biomarkers that predict therapeutic response can guide the choice of treatment modality and improve patient outcomes. We applied the bulk gene expression deconvolution methods and BayesNMF with consensus hierarchical clustering on 1058 primary breast cancer samples from The Cancer Genome Atlas (TCGA) to identify seven bulk expression subtypes (B1-B7) and five cancer cell-specific expression subtypes (C1-C5). Integrative genomic analysis characterized the subtypes and identified candidate subtype-associated therapeutic targets. Projection of cancer cell-specific subtypes to cell lines allowed us to predict subtype-specific cancer vulnerabilities. Cancer cell-specific subtype 5 (C5)-associated cell lines are predicted to be vulnerable to CDK6 and TPI1 inhibition. As a forward translation, we also developed the NMF models for predicting CDK4 and CDK6 dependency in TCGA BRCA samples by training the models with gene expression features and dependency scores in the Dependency Map (DepMap) cell lines. C4 showed CDK4 dependency and C5 showed CDK6 dependency. Overall, our BayesNMF consensus hierarchical clustering based on cancer cell-specific expression profiles identified robust TCGA BRCA expression subtypes and the reverse and forward translation between human tumor tissues and cell lines allowed us to predict subtype-specific vulnerabilities.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"267"},"PeriodicalIF":6.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753928","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}

{"title":"The role of the gut microbiota in chemotherapy response, efficacy and toxicity: a systematic review.","authors":"Doortje Böhm, Emma Russ, Henk-Jan Guchelaar, Janine Ziemons, John Penders, Marjolein L Smidt, Niels van Best, Maarten J Deenen","doi":"10.1038/s41698-025-01034-0","DOIUrl":"10.1038/s41698-025-01034-0","url":null,"abstract":"<p><p>There is growing evidence for the relationship between the gut microbiota and the effect of chemotherapy. Therefore, this systematic review provides an overview of the current evidence on the effects of the gut microbiota on chemotherapy response, efficacy and toxicity in patients with cancer. PubMed, Web of Science, and EMBASE were searched to collect studies on cancer patients treated with chemotherapy that evaluated tumor response, efficacy, or toxicity, and included microbiome analysis through fecal samples. A total of 22 studies were included. Bacteria associated with better response in lung tumors were, amongst others, a relatively higher abundance of Streptococcus mutans, Enterococcus casseliflavus, and Bacteroides, while bacteria linked to response in gastrointestinal tumors included, among others, higher relative abundances of Lactobacillaceae, Bacteroides fragilis, and Roseburia faecis. Distinctive bacterial taxa were associated with clinical therapy, although causality was not proven. Targeting the gut microbiota during chemotherapy is considered to be a promising approach to enhance the response and to prevent toxicity of chemotherapy.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"265"},"PeriodicalIF":6.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753930","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}

{"title":"Predicting ROS1 and ALK fusions in NSCLC from H&E slides with a two-step vision transformer approach.","authors":"Eghbal Amidi, Mohammadreza Ramzanpour, Ming Chen, Tommy Boucher, Mukund Varma, Timothy Samec, Brian Lamon, Nicolas Stransky, Mark R Miglarese, Matthew Oberley, David Spetzler, George W Sledge","doi":"10.1038/s41698-025-01037-x","DOIUrl":"10.1038/s41698-025-01037-x","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) is one of the deadliest and most prevalent cancers worldwide, with 5-year survival rates of ~28%. The molecular heterogeneity within NSCLC encompasses several types of genetic alterations, such as mutations, amplifications, and rearrangements, and can drive aggressive tumor behavior and poor response to therapy. Among these genetic alterations are ALK and ROS1 fusions. Though these fusion events are relatively rare, their identification is crucial for selecting effective targeted treatments and avoiding therapies with significant side-effects. Fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and sequencing of DNA and RNA are standard methods to detect ALK and ROS1 fusions, but they are costly, time-consuming, and require adequate tumor tissue. Here we employ deep learning models using whole slide images (WSIs) of hematoxylin and eosin (H&E)-stained formalin-fixed paraffin embedded (FFPE) NSCLC tumor specimens to identify tumors most likely to harbor ALK and ROS1 fusions in a cohort of 33,014 patients, out of which 306 and 697 patients are positive for ROS1 or ALK fusions, respectively. A vision transformer model (MoCo-V3) was trained as a feature extractor, followed by training transformer-based models to predict the presence of ROS1 and ALK fusions. Due to the limited positive sample size for ROS1, a two-step specialized training procedure was implemented to enhance prediction performance during cross-validation. Our approach achieved receiver-operating characteristic areas under the curves (ROC AUCs) of 0.85 for ROS1 and 0.84 for ALK on a holdout dataset, demonstrating the effectiveness of this method. This framework holds significant potential for clinical application by offering a scalable, accurate, and cost-efficient method for detecting ALK and ROS1 fusions. Furthermore, it may serve as a pre-screening tool to identify candidates for confirmatory diagnostic testing and clinical trials, ultimately improving the efficiency of selecting appropriately targeted therapies for NSCLC patients.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"266"},"PeriodicalIF":6.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753929","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}

{"title":"Enhancing adoptive cell therapy: future strategies for immune cell radioprotection in neuro-oncology.","authors":"Abigail J Groth, Mustafa Khasraw, James D Byrne, Zachary J Reitman","doi":"10.1038/s41698-025-01059-5","DOIUrl":"10.1038/s41698-025-01059-5","url":null,"abstract":"<p><p>Adoptive cell therapy (ACT), particularly chimeric antigen receptor T cell (CAR T) therapy, has emerged as a promising approach in cancer treatment, demonstrating efficacy in hematological malignancies but facing challenges in brain tumors. The combination of ACT with radiation therapy (RT) offers a potential strategy to enhance therapeutic outcomes, as RT can stimulate immune responses by promoting antigen presentation and T cell recruitment. However, a major hurdle is the radiosensitivity of immune cells, leading to their rapid depletion within the radiation field, which undermines the benefits of this combination. This review explores strategies to increase the radioresistance of immune cells, highlighting the need for innovative radioprotective approaches. We discuss the potential of extremophile-derived molecules, such as the Damage Suppressor protein from tardigrades, as novel radioprotectants that could be integrated into ACT protocols. Furthermore, we address key considerations for clinical trial design, including the sequencing of RT and ACT, dosing parameters, and safety considerations. By bridging insights from extremophile biology and immuno-oncology, this work aims to optimize the efficacy of ACT in the challenging context of brain tumors, paving the way for enhanced treatment strategies in neuro-oncology.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"264"},"PeriodicalIF":6.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144743345","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}

{"title":"Targeting TNFAIP2 with NIR-II CRISPR-Cas9 nanosystem to overcome cisplatin resistance in laryngeal cancer.","authors":"Xiaoli Li, Jiashuo Wang, Jiaxing Guo, Ming Zhang","doi":"10.1038/s41698-025-01054-w","DOIUrl":"10.1038/s41698-025-01054-w","url":null,"abstract":"<p><p>Cisplatin resistance is a major challenge in laryngeal cancer treatment. Tumor necrosis factor-alpha-induced protein 2 (TNFAIP2) has been implicated in chemoresistance, though its role in laryngeal cancer remains unclear. We identified TNFAIP2 as a key gene associated with cisplatin resistance and developed a second near-infrared (NIR-II) light-responsive CRISPR-Cas9 nanosystem (APC@RBCs) to target it. In cisplatin-resistant Tu177/CDDP cells, light-activated knockout of TNFAIP2 significantly increased cisplatin sensitivity (IC50 reduced from 12.55 to 4.37 µg/mL). Mechanistic studies revealed that TNFAIP2 modulates cisplatin resistance via the NRF2 pathway, affecting oxidative stress response and epithelial-mesenchymal transition. TNFAIP2 deletion also suppressed cancer cell migration and invasion. Our results establish TNFAIP2 as a critical mediator of chemoresistance and demonstrate the potential of APC@RBCs as a precise, non-invasive gene therapy platform. This strategy offers a promising approach to overcoming cisplatin resistance and improving treatment outcomes in laryngeal cancer patients.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"263"},"PeriodicalIF":6.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144743346","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}

{"title":"Comprehensive identification of NRG1 fusions in 25,203 patients with solid tumors.","authors":"Shui Xiang, Yiwen Zheng, Mengxiao Wang, Xuewen Liu, Xing Zhang, Dongsheng Chen, Guangxian Meng, Hongtao Xu, Xiaoxuan Wang","doi":"10.1038/s41698-025-01044-y","DOIUrl":"10.1038/s41698-025-01044-y","url":null,"abstract":"<p><p>NRG1 fusion is an emerging oncogenic driver, and the FDA has approved drugs for the treatment of non-small cell lung cancer and pancreatic cancer associated with NRG1 fusions. This study retrospectively analyzed data from 25,203 patients with solid tumors who underwent next-generation sequencing (NGS) and identified 49 patients with NRG1 fusions. The mutation profiles and actionable therapeutic targets were analyzed among patients with fusions. In this study, 0.2% (49/25,203) of patients harbored NRG1 fusions. The frequencies of NRG1 fusions across various cancer types were as follows: prostate cancer, 0.65%; breast cancer, 0.47%; lung cancer, 0.29%; esophageal cancer, 0.25%; colorectal cancer, 0.17%; gastric cancer, 0.13%; pancreatic cancer, 0.11%; and hepatocellular carcinoma, 0.05%). A total of 36 fusion partners were detected, among which CD74 was predominant, accounting for 29.3% of cases. Patients with NRG1 fusions presented a greater frequency of FGFR1 mutations and RET fusions, compared with non-NRG1 fusion patients. Most lung cancer and colorectal cancer patients with NRG1 fusions harbored FDA-approved or potential drug targets, whereas those diagnosed with breast cancer harbored fewer such targets. NRG1 fusion-related drugs can provide additional treatment options. Our study expands the NRG1 fusion gene landscape and provides a valuable reference for the comprehensive treatment of patients with NRG1 fusions.</p>","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"262"},"PeriodicalIF":6.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144743344","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}