NPJ Precision Oncology最新文献_第2页

Multi-omics analysis identifies glioblastoma dependency on H3K9me3 methyltransferase activity.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-20 DOI: 10.1038/s41698-025-00829-5

Qiqi Xie, Yuanning Du, Sugata Ghosh, Saranya Rajendran, Aaron A Cohen-Gadol, José-Manuel Baizabal, Kenneth P Nephew, Leng Han, Jia Shen

{"title":"Multi-omics analysis identifies glioblastoma dependency on H3K9me3 methyltransferase activity.","authors":"Qiqi Xie, Yuanning Du, Sugata Ghosh, Saranya Rajendran, Aaron A Cohen-Gadol, José-Manuel Baizabal, Kenneth P Nephew, Leng Han, Jia Shen","doi":"10.1038/s41698-025-00829-5","DOIUrl":"10.1038/s41698-025-00829-5","url":null,"abstract":"Histone H3 lysine 9 dimethylation and trimethylation (H3K9me2/3) are prevalent in human genomes, especially in heterochromatin and specific euchromatic genes. Methylation of H3K9 is modulated by enzymes such as SUV39H1, SUV39H2, SETDB1, SETDB2, and EHMT1/2, which influence cancer progression. This study reveals differential expression of these six H3K9 methyltransferases in tumors, with SUV39H1, SUV39H2, and SETDB1 showing significant links to cancer phenotypes. We developed the \"H3K9me3 MtSig\" (H3K9me3 methyltransferases signature) based on these findings. H3K9me3 MtSig is unique to various tumors, with prognostic significance and associations with key signaling pathways, especially in glioblastoma (GBM). Elevated H3K9me3 MtSig was observed in GBM samples, correlating with the G2/M cell cycle and reduced immune responses. H3K9me3-mediated repetitive sequence silencing by H3K9me3 MtSig contributed to these phenotypes, and inhibiting H3K9me3 MtSig in patient-derived GBM cells suppressed proliferation and increased immune responses. H3K9me3 MtSig serves as an independent prognostic factor and potential therapeutic target.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"78"},"PeriodicalIF":6.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670441","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

Real-time image fusion and Apple Vision Pro in laparoscopic microwave ablation of hepatic hemangiomas.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-20 DOI: 10.1038/s41698-025-00867-z

Tao Lan, Sichun Liu, Yihe Dai, Jia Luo, Jiang Han, Yun Jin

{"title":"Real-time image fusion and Apple Vision Pro in laparoscopic microwave ablation of hepatic hemangiomas.","authors":"Tao Lan, Sichun Liu, Yihe Dai, Jia Luo, Jiang Han, Yun Jin","doi":"10.1038/s41698-025-00867-z","DOIUrl":"10.1038/s41698-025-00867-z","url":null,"abstract":"Laparoscopic ultrasound-guided liver microwave ablation requires precise navigation and spatial accuracy. We developed an image fusion navigation system that integrates laparoscopic, ultrasound, and 3D liver model images into a unified real-time visualization. The Apple Vision Pro mixed reality device projects all essential image information into the surgeon's field of view in real-time. This system reduces cognitive load and enhances surgical precision and efficiency. Comparative experiments showed a significant improvement in puncture accuracy under AVP guidance (success rate of 90%) compared to traditional methods (42.5%), benefiting both novice and experienced surgeons. According to the NASA Task Load Index evaluation, the system also reduced the workload of surgeons. In eight patients, ablation was successful with minimal blood loss, no major complications, and rapid recovery. Despite challenges such as cost and fatigue, these results highlight the potential of mixed reality technology to improve spatial navigation, reduce cognitive demands, and optimize complex surgical procedures.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"79"},"PeriodicalIF":6.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670443","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

Prediction and analysis of tumor infiltrating lymphocytes across 28 cancers by TILScout using deep learning.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-19 DOI: 10.1038/s41698-025-00866-0

Huibo Zhang, Lulu Chen, Lan Li, Yang Liu, Barnali Das, Shuang Zhai, Juan Tan, Yan Jiang, Simona Turco, Yi Yao, Dmitrij Frishman

{"title":"Prediction and analysis of tumor infiltrating lymphocytes across 28 cancers by TILScout using deep learning.","authors":"Huibo Zhang, Lulu Chen, Lan Li, Yang Liu, Barnali Das, Shuang Zhai, Juan Tan, Yan Jiang, Simona Turco, Yi Yao, Dmitrij Frishman","doi":"10.1038/s41698-025-00866-0","DOIUrl":"10.1038/s41698-025-00866-0","url":null,"abstract":"The density of tumor-infiltrating lymphocytes (TILs) serves as a valuable indicator for predicting anti-tumor responses, but its broad impact across various types of cancers remains underexplored. We introduce TILScout, a pan-cancer deep-learning approach to compute patch-level TIL scores from whole slide images (WSIs). TILScout achieved accuracies of 0.9787 and 0.9628, and AUCs of 0.9988 and 0.9934 in classifying WSI patches into three categories-TIL-positive, TIL-negative, and other/necrotic-on validation and independent test sets, respectively, surpassing previous studies. The biological significance of TILScout-derived TIL scores across 28 cancers was validated through comprehensive functional and correlational analyses. A consistent decrease in TIL scores with an increase in cancer stage provides direct evidence that the lower TIL content may stimulate cancer progression. Additionally, TIL scores correlated with immune checkpoint gene expression and genomic variation in common cancer driver genes. Our comprehensive pan-cancer survey highlights the critical prognostic significance of TILs within the tumor microenvironment.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"76"},"PeriodicalIF":6.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664083","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

Revealing neuroendocrine transformation in gynecological cancers through genomic analysis.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-19 DOI: 10.1038/s41698-025-00861-5

Ann Oluloro, David L Wells, Charles K Childers, Tiffany Luu, Keith D Eaton, Renata R Urban, Eric Q Konnick, Vera A Paulson, Kalyan Banda

{"title":"Revealing neuroendocrine transformation in gynecological cancers through genomic analysis.","authors":"Ann Oluloro, David L Wells, Charles K Childers, Tiffany Luu, Keith D Eaton, Renata R Urban, Eric Q Konnick, Vera A Paulson, Kalyan Banda","doi":"10.1038/s41698-025-00861-5","DOIUrl":"10.1038/s41698-025-00861-5","url":null,"abstract":"Neuroendocrine transformation (NT) in cancers, typically observed under the selective pressure of targeted therapies, involves lineage plasticity where adenocarcinomas adopt neuroendocrine characteristics while retaining the molecular alterations of their original histology. This phenomenon, well-documented in prostate and lung cancers, has not been observed in gynecological malignancies until now. We present two pivotal cases involving primary ovarian and uterine cancers that developed neuroendocrine carcinomas post-treatment. Initially presumed to be independent primaries, comprehensive next-generation sequencing technologies, including UW-OncoPlex and BROCA panels, were used to establish a clonal relationship between the primary tumors and their respective neuroendocrine metastases. This report provides the first documented instances of NT in gynecological cancers, indicating that it may be a more widespread resistance mechanism than previously recognized. Routine re-biopsy and early integration of advanced molecular diagnostics into clinical practice will identify NT and provide insights into pathogenesis and eventual therapeutic options.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"77"},"PeriodicalIF":6.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664085","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

Uncovering the genetic variation spectrum of colorectal polyposis from a multicentre cohort in China. 从中国多中心队列中揭示结直肠息肉病的遗传变异谱。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-15 DOI: 10.1038/s41698-025-00864-2

Mengyuan Yang, Ding Zhang, Zhijun Yuan, Daici Chen, Haixing Ju, Bin Wu, Jie Pan, Guoli Gu, Yuehong Cui, Yanhong Gu, Dong Xu, Ying Yuan

{"title":"Uncovering the genetic variation spectrum of colorectal polyposis from a multicentre cohort in China.","authors":"Mengyuan Yang, Ding Zhang, Zhijun Yuan, Daici Chen, Haixing Ju, Bin Wu, Jie Pan, Guoli Gu, Yuehong Cui, Yanhong Gu, Dong Xu, Ying Yuan","doi":"10.1038/s41698-025-00864-2","DOIUrl":"10.1038/s41698-025-00864-2","url":null,"abstract":"This multicentre study addresses the genetic spectrum of colorectal polyposis in China. We analyzed 120 patients with over 10 adenomas using a 139-gene next-generation sequencing panel and multiplex ligation-dependent probe amplification. Findings revealed that 89 patients carried pathogenic germline variants, primarily in the APC gene. Notably, one patient had both APC and BRCA2 variants from different parental lines. Our results indicate a higher APC mutation rate compared to prior studies, primarily consisting of nonsense mutations. This research represents the first multicentre clinical investigation in China, highlighting significant differences in mutation profiles compared to the study conducted by the research team from Germany. Since patients were categorized by adenoma count, with none in the 10-19 range diagnosed with hereditary tumors, we recommend delaying genetic testing for those with fewer than 20 adenomas, while emphasizing the need for prompt testing for higher counts.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"75"},"PeriodicalIF":6.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634277","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

Deep learning models in classifying primary bone tumors and bone infections based on radiographs.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-13 DOI: 10.1038/s41698-025-00855-3

Hua Wang, Yu He, Lu Wan, Chenbei Li, Zhaoqi Li, Zhihong Li, Haodong Xu, Chao Tu

{"title":"Deep learning models in classifying primary bone tumors and bone infections based on radiographs.","authors":"Hua Wang, Yu He, Lu Wan, Chenbei Li, Zhaoqi Li, Zhihong Li, Haodong Xu, Chao Tu","doi":"10.1038/s41698-025-00855-3","DOIUrl":"10.1038/s41698-025-00855-3","url":null,"abstract":"Primary bone tumors (PBTs) present significant diagnostic challenges due to their heterogeneous nature and similarities with bone infections. This study aimed to develop an ensemble deep learning framework that integrates multicenter radiographs and extensive clinical features to accurately differentiate between PBTs and bone infections. We compared the performance of the ensemble model with four imaging models based solely on radiographs utilizing EfficientNet B3, EfficientNet B4, Vision Transformer, and Swin Transformers. The patients were split into external dataset (N = 423) and internal dataset [including training (N = 1044), test (N = 354), and validation set (N = 171)]. The ensemble model outperformed imaging models, achieving areas under the curve (AUCs) of 0.948 and 0.963 on internal and external sets, respectively, with accuracies of 0.881 and 0.895. Its performance surpassed junior and mid-level radiologists and was comparable to senior radiologists (accuracy: 83.6%). These findings underscore the potential of deep learning in enhancing diagnostic precision for PBTs and bone infections (Research Registration Unique Identifying Number (UIN): researchregistry10483 and with details are available at https://www.researchregistry.com/register-now#home/registrationdetails/6693845995ba110026aeb754/ ).","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"72"},"PeriodicalIF":6.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616582","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

Lethal co-expression intolerance underlies the mutually exclusive expression of ASCL1 and NEUROD1 in SCLC cells. ASCL1和NEUROD1在SCLC细胞中的相互排斥表达是致命的共表达不耐受性的基础。

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-13 DOI: 10.1038/s41698-025-00860-6

Hirofumi Watanabe, Yusuke Inoue, Kazuo Tsuchiya, Kazuhiro Asada, Makoto Suzuki, Hiroshi Ogawa, Masayuki Tanahashi, Takuya Watanabe, Shun Matsuura, Kazuyo Yasuda, Ippei Ohnishi, Shiro Imokawa, Hideki Yasui, Masato Karayama, Yuzo Suzuki, Hironao Hozumi, Kazuki Furuhashi, Noriyuki Enomoto, Tomoyuki Fujisawa, Kazuhito Funai, Kazuya Shinmura, Haruhiko Sugimura, Naoki Inui, Takafumi Suda

{"title":"Lethal co-expression intolerance underlies the mutually exclusive expression of ASCL1 and NEUROD1 in SCLC cells.","authors":"Hirofumi Watanabe, Yusuke Inoue, Kazuo Tsuchiya, Kazuhiro Asada, Makoto Suzuki, Hiroshi Ogawa, Masayuki Tanahashi, Takuya Watanabe, Shun Matsuura, Kazuyo Yasuda, Ippei Ohnishi, Shiro Imokawa, Hideki Yasui, Masato Karayama, Yuzo Suzuki, Hironao Hozumi, Kazuki Furuhashi, Noriyuki Enomoto, Tomoyuki Fujisawa, Kazuhito Funai, Kazuya Shinmura, Haruhiko Sugimura, Naoki Inui, Takafumi Suda","doi":"10.1038/s41698-025-00860-6","DOIUrl":"10.1038/s41698-025-00860-6","url":null,"abstract":"Small cell lung cancer (SCLC) subtypes, defined by the expression of lineage-specific transcription factors (TFs), are thought to be mutually exclusive, with intra-tumoral heterogeneities. This study investigated the mechanism underlying this phenomenon with the aim of identifying a novel vulnerability of SCLC. We profiled the expression status of ASCL1, NEUROD1, POU2F3, and YAP1 in 151 surgically obtained human SCLC samples. On subtyping, a high degree of mutual exclusivity was observed between ASCL1 and NEUROD1 expression at the cell, but not tissue, level. Inducible co-expression models of all combinations of ASCL1, NEUROD1, POU2F3, YAP1, and ATOH1 using SCLC cell lines showed that some expression combinations, such as ASCL1 and NEUROD1, exhibited mutual repression and caused growth inhibition and apoptosis. Gene expression and ATAC-seq analyses of the ASCL1 and NEUROD1 co-expression models revealed that co-expression of ASCL1 in NEUROD1-driven cells, and of NEUROD1 in ASCL1-driven cells, both (although more efficiently by the former) reprogrammed the cell lineage to favor the ectopically expressed factor, with rewiring of chromatin accessibility. Mechanistically, co-expressed NEUROD1 in ASCL1-driven SCLC cells caused apoptosis by downregulating BCL2, likely in a MYC-independent manner. In conclusion, lethal co-expression intolerance underlies the mutual exclusivity between these pioneer TFs, ASCL1 and NEUROD1, in an SCLC cell. Further investigation is warranted to enable therapeutic targeting of this vulnerability.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"74"},"PeriodicalIF":6.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625542","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-omics analysis to uncover the molecular basis of tumor budding in head and neck squamous cell carcinoma.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-13 DOI: 10.1038/s41698-025-00856-2

Iordanis Ourailidis, Fabian Stögbauer, Yuxiang Zhou, Susanne Beck, Eva Romanovsky, Stephan Eckert, Barbara Wollenberg, Markus Wirth, Katja Steiger, Bernhard Kuster, Olivier Gires, Albrecht Stenzinger, Peter Schirmacher, Wilko Weichert, Peer-Hendrik Kuhn, Melanie Boxberg, Jan Budczies

{"title":"Multi-omics analysis to uncover the molecular basis of tumor budding in head and neck squamous cell carcinoma.","authors":"Iordanis Ourailidis, Fabian Stögbauer, Yuxiang Zhou, Susanne Beck, Eva Romanovsky, Stephan Eckert, Barbara Wollenberg, Markus Wirth, Katja Steiger, Bernhard Kuster, Olivier Gires, Albrecht Stenzinger, Peter Schirmacher, Wilko Weichert, Peer-Hendrik Kuhn, Melanie Boxberg, Jan Budczies","doi":"10.1038/s41698-025-00856-2","DOIUrl":"10.1038/s41698-025-00856-2","url":null,"abstract":"Tumor budding (TB) is a prognostic biomarker in HPV-negative and HPV-positive head and neck squamous cell carcinoma (HNSCC). Analyzing TCGA and CPTAC mutation, RNA, and RPPA data and performing proteomics and IHC in two independent in-house cohorts, we uncovered molecular correlates of TB in an unprecedentedly comprehensive manner. NSD1 mutations were associated with lower TB in HPV-negative HNSCC. Comparing budding and nonbudding tumors, 66 miRNAs, including the miRNA-200 family, were differentially expressed in HPV-negative HNSCC. 3,052 (HPV-negative HNSCC) and 360 (HPV-positive HNSCC) RNAs were differentially expressed. EMT, myogenesis, and other cancer hallmarks were enriched in the overexpressed RNAs. In HPV-negative HNSCC, 88 proteins were differentially expressed, significantly overlapping with the differentially expressed RNAs. CAV1 and MMP14 protein expression investigated by IHC increased gradually from nonbudding tumors to the bulk of budding tumors and tumor buds. The molecular insights gained support new approaches to therapy development and guidance for HNSCC.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"73"},"PeriodicalIF":6.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625552","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

Exosomes containing miR-152-3p targeting FGFR3 mediate SLC7A7-induced angiogenesis in bladder cancer.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-12 DOI: 10.1038/s41698-025-00859-z

Chun Cao, Yu Wang, Xiaolin Deng, Xinlei Zhao, Yuwen Chen, Wanlong Tan, Fan Deng, Fei Li

{"title":"Exosomes containing miR-152-3p targeting FGFR3 mediate SLC7A7-induced angiogenesis in bladder cancer.","authors":"Chun Cao, Yu Wang, Xiaolin Deng, Xinlei Zhao, Yuwen Chen, Wanlong Tan, Fan Deng, Fei Li","doi":"10.1038/s41698-025-00859-z","DOIUrl":"10.1038/s41698-025-00859-z","url":null,"abstract":"Bladder cancer (BCa) is a prevalent malignancy with a poor prognosis. SLC7A7 has been linked to BCa progression and angiogenesis, but its specific role remains unclear. We established a SLC7A7-knockdown BCa cell line to investigate its effects on angiogenesis. In vivo experiments assessed tumor vascularization, while in vitro studies explored exosome involvement. MiRNA sequencing identified miR-152-3p as a key regulator. Further investigation using dual-luciferase reporter assays, qRT-PCR, and Western blot revealed that miR-152-3p inhibits the expression of FGFR3 by binding to its 3' UTR. Meanwhile, functional assays, including angiogenesis assays, Transwell assays, and wound healing assays, were performed to evaluate the effects of miR-152-3p on angiogenesis. We confirmed the significant role of SLC7A7 in BCa progression, specifically in promoting angiogenesis, through the involvement of exosomes and the regulatory axis of miR-152-3p/ FGFR3. Targeting FGFR3 might be a promising strategy to reverse control BCa progression for an improved prognosis.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"71"},"PeriodicalIF":6.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616584","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

Targeting USP8 causes synthetic lethality through degradation of FGFR2 in ARID1A-deficient ovarian clear cell carcinoma.

IF 6.8 1区医学

NPJ Precision Oncology Pub Date : 2025-03-12 DOI: 10.1038/s41698-025-00850-8

Ryosuke Saito, Makoto Fukushima, Mariko Sasaki, Aikou Okamoto, Hideaki Ogiwara

{"title":"Targeting USP8 causes synthetic lethality through degradation of FGFR2 in ARID1A-deficient ovarian clear cell carcinoma.","authors":"Ryosuke Saito, Makoto Fukushima, Mariko Sasaki, Aikou Okamoto, Hideaki Ogiwara","doi":"10.1038/s41698-025-00850-8","DOIUrl":"10.1038/s41698-025-00850-8","url":null,"abstract":"Over half of ovarian clear cell carcinoma (OCCC) cases exhibit deficiencies in the ARID1A gene, a chromatin remodeling complex component. OCCC is resistant to chemotherapy and challenging to treat, necessitating new drug treatment strategies. This study used a publicly available dependency factor database to identify synthetic lethal targets for ARID1A-deficient cancer. The DepMap portal was used to identify genes on which ARID1A-deficient cancer cell lines are highly dependent. Our analysis limited to ovarian cancer cell lines only identified the deubiquitinating enzyme USP8 as a synthetic lethal target in ARID1A-deficient OCCC cancer cell lines and mouse xenograft models. In addition, USP8 inhibitors were more selective for ARID1A-deficient cells than existing candidate drugs used in promising clinical trials for ARID1A-deficient cancers. Suppression of USP8 in ARID1A-deficient cells led to degradation of FGFR2 via the proteasome. Deficiency of ARID1A causes abnormalities in the STAT3 pathway, which is one of the downstream pathways of FGFR2, but suppression of USP8 attenuates phosphorylation of STAT3 pT705 and induces apoptosis. Taken together, our data suggest that USP8 is a novel therapeutic target for ARID1A-deficient OCCC and that USP8 inhibitors suppress FGFR2-STAT3 signaling.","PeriodicalId":19433,"journal":{"name":"NPJ Precision Oncology","volume":"9 1","pages":"69"},"PeriodicalIF":6.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616587","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