Cancer Science最新文献_第10页

Targeting the NR3C1-ACSL4 Axis Triggers Ferroptosis to Overcome Radioresistance in Prostate Cancer. 靶向NR3C1-ACSL4轴触发铁下垂克服前列腺癌放射耐药

IF 4.3 2区医学

Cancer Science Pub Date : 2026-07-23 DOI: 10.1111/cas.70479

Jing Yang, Puyuan Chen, Yawen Zheng, Feiyue Shi, Min Wang, Luwei Xu, Xiaowei Wei, Xiumei Wang

{"title":"Targeting the NR3C1-ACSL4 Axis Triggers Ferroptosis to Overcome Radioresistance in Prostate Cancer.","authors":"Jing Yang, Puyuan Chen, Yawen Zheng, Feiyue Shi, Min Wang, Luwei Xu, Xiaowei Wei, Xiumei Wang","doi":"10.1111/cas.70479","DOIUrl":"10.1111/cas.70479","url":null,"abstract":"Radioresistance in prostate cancer demands innovative sensitization strategies. We identified the glucocorticoid receptor nuclear receptor subfamily 3 group C member 1 (NR3C1) as a key negative regulator of radiosensitivity linked to poor prognosis. NR3C1 transcriptionally upregulates the lipid-metabolizing enzyme, acyl-CoA synthetase long-chain family member 4 (ACSL4), thereby enhancing cell proliferation, migration, and radioresistance. High ACSL4 expression sensitizes cells to ferroptosis inducers that amplify lipid peroxidation and restore radiosensitivity. Using the clinically applicable ferroptosis inducer, dihydroartemisinin (DHA), we found that DHA synergizes with ACSL4 to trigger ferroptosis, sensitizing radioresistant cells and xenografts to radiation. This effect was characterized by elevated lipid peroxidation and was reversed by the ferroptosis inhibitor deferoxamine. Collectively, our study revealed that the NR3C1-ACSL4 axis regulates lipid peroxidation and promotes radioresistance. Targeting this axis with DHA and using ACSL4 as a biomarker represents a promising preclinical strategy to overcome radioresistance in prostate cancer, pending further clinical validation.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13395388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148580936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Epidemiological and Prognostic Differences in Malignant Mesothelioma Between Eastern China and SEER Database. 中国东部地区与SEER数据库间恶性间皮瘤的流行病学及预后差异。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-07-21 DOI: 10.1111/cas.70481

Ningning Li, Ruting Wang, Wenya Zhang, Zulei Shao, Hongyu Lin, Guanai Bao, Weimin Mao, Zhongjian Chen

{"title":"Epidemiological and Prognostic Differences in Malignant Mesothelioma Between Eastern China and SEER Database.","authors":"Ningning Li, Ruting Wang, Wenya Zhang, Zulei Shao, Hongyu Lin, Guanai Bao, Weimin Mao, Zhongjian Chen","doi":"10.1111/cas.70481","DOIUrl":"10.1111/cas.70481","url":null,"abstract":"Eastern China malignant mesothelioma (MM) presents distinct features-younger age, female predominance, and moremalignant peritoneal mesothelioma (MPeM)-contrasting with the Western profile of older males with malignant pleural mesothelioma (MPM). Robust survival data for this population are still unavailable. This retrospective study included 253 MM patients from Zhejiang Cancer Hospital (2010-2024; 222 from Zhejiang Province, ZJ cohort) to update regional epidemiology and compare survival with the Surveillance, Epidemiology, and End Results program (SEER). The ZJ cohort exhibited a younger median age at diagnosis (58 vs. 74 years), a higher proportion of females (62% vs. 24%), and a higher prevalence of MPeM (54% vs. 11%) relative to the SEER cohort. Overall survival (OS) was significantly prolonged in the ZJ cohort (median OS: 22 vs. 10 months), with survival benefits consistently observed across sex, age, and MPM subgroups. Multivariate Cox analysis revealed age as the only consistent independent prognostic factor in both ZJ and SEER cohorts. Following propensity score matching to minimize confounding, the ZJ cohort maintained a significantly longer survival in MPM but exhibited worse outcome in MPeM relative to SEER. Collectively, this study not only updated epidemiologic features for MM in Eastern China but also reported the unique survival patterns, uncovering inter-population heterogeneity. These findings emphasize the value of region-specific prognostic evidence and the limitations of directly applying Western data to Asian populations.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

MEN1 Deficiency Drives Lung Cancer Progression via Activation of MMP10-Mediated Angiogenesis. MEN1缺乏通过激活mmp10介导的血管生成驱动肺癌进展。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-07-21 DOI: 10.1111/cas.70470

Chengyu Wei, Xiangyu Liu, Shimin Hu, Xiaodie Shen, Yingli Liu, Xinxin Qin, Ye Zhou, Jianqi Zheng, Bingke Tian, Jingfang Hong, Yongxia Song, Di Wang, Linlin Peng, Jinxia Ding, Fang Wang, Hui Zhang, Shihao Zhang, Huan Qiu

{"title":"MEN1 Deficiency Drives Lung Cancer Progression via Activation of MMP10-Mediated Angiogenesis.","authors":"Chengyu Wei, Xiangyu Liu, Shimin Hu, Xiaodie Shen, Yingli Liu, Xinxin Qin, Ye Zhou, Jianqi Zheng, Bingke Tian, Jingfang Hong, Yongxia Song, Di Wang, Linlin Peng, Jinxia Ding, Fang Wang, Hui Zhang, Shihao Zhang, Huan Qiu","doi":"10.1111/cas.70470","DOIUrl":"10.1111/cas.70470","url":null,"abstract":"Angiogenesis is essential for tumor progression, MEN1 gene encodes the menin protein, which is known as a tumor suppressor in lung tissue. Our previous study have shown that vascular density is significantly increased in menin-deficient lung cancer, suggesting that menin deficiency may promote the malignant progression of lung cancer by enhancing angiogenesis. However, whether menin play an important role in angiogenesis of lung cancer and the underlying mechanisms remain unclear. In this study, lung-specific KrasG12D mutation induced mouse lung cancer model, clinical human lung cancer tissues, lung cancer and vascular endothelial cell lines were utilized, RNA-seq, ATAC-seq, ChIP, tube formation, sprouting, invasion and migration experiments were applied to investigate the role and mechanism of MEN1 in lung cancer angiogenesis. The result show menin were negatively related to angiogenesis markers and phenotype. Menin deficiency indirectly upregulates MMP10 transcription through activation of the transcription factor JunD. The expression of MMP10 further activates the EGFR receptor in vascular endothelial cells, thereby initiating the AKT/ERK signaling pathway. Inhibition MMP10 reversed menin low expression induce angiogenic phenotype and tumor progress. In conclusion, menin deficiency promotes angiogenesis through upregulates MMP10, targeting MMP10 with inhibitor represent an effective anti-angiogenic strategy for treating MEN1-deficient lung cancer.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

SERPINE1 Alternative Polyadenylation Influences Gastric Cancer Prognosis via N6-Methyladenosine Modification. SERPINE1选择性聚腺苷化通过n6 -甲基腺苷修饰影响胃癌预后

IF 4.3 2区医学

Cancer Science Pub Date : 2026-07-20 DOI: 10.1111/cas.70464

Zhuoyi Wu, Ruyun Xu, Ju Fang, Bing Liu, Cao Zhang, Shangxin Zhang, Jing Ni

{"title":"SERPINE1 Alternative Polyadenylation Influences Gastric Cancer Prognosis via N6-Methyladenosine Modification.","authors":"Zhuoyi Wu, Ruyun Xu, Ju Fang, Bing Liu, Cao Zhang, Shangxin Zhang, Jing Ni","doi":"10.1111/cas.70464","DOIUrl":"10.1111/cas.70464","url":null,"abstract":"Alternative polyadenylation (APA) and N6-methyladenosine (m6A) methylation are critical post-transcriptional regulators in cancer, yet their synergistic role in gastric cancer (GC) remains poorly understood. By integrating RNA-seq and MeRIP-seq data from paired GC tumor and adjacent normal tissues, we identified 9769 distinct APA events and 3117 differentially methylated sites. Concurrent 3'UTR length and methylation alterations were observed in 165 genes. Among these, SERPINE1 emerged as an independent prognostic factor; its high expression correlated with advanced TNM stages and poor survival across multiple independent cohorts. Moreover, elevated plasma SERPINE1 protein levels in an in-house cohort of 263 GC patients were significantly associated with worse overall and disease-specific survival. Mechanistically, the APA factor CSTF2 and the m6A reader IGF2BP1 were found to physically interact and cooperatively regulate SERPINE1 3'UTR selection. Silencing either factor shifted expression toward the long 3'UTR isoform and reduced SERPINE1 protein levels. Functional assays further confirmed that the short SERPINE1 isoform promotes GC cell proliferation, migration, and invasion more potently than the long isoform. Collectively, this study reveals that CSTF2 and IGF2BP1 synergistically drive SERPINE1 3'UTR shortening to enhance GC malignancy, highlighting SERPINE1 as a promising prognostic biomarker and potential therapeutic target.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Evidence That the Protein Phosphatase Activity of PTEN Contributes to Embryonic Development and Tumor Suppression. PTEN蛋白磷酸酶活性参与胚胎发育和肿瘤抑制的证据。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-07-19 DOI: 10.1111/cas.70476

Priyanka Tibarewal, Laura Spinelli, Nisha Kriplani, Helen Wise, Nadege Poncet, Giulia Marzano, Karen E Anderson, Katarzyna M Grzes, Zofia Varyova, Mahreen Adil, C Peter Downes, Phillip T Hawkins, Len R Stephens, Kate G Storey, Doreen A Cantrell, Bart Vanhaesebroeck, Nicholas R Leslie

{"title":"Evidence That the Protein Phosphatase Activity of PTEN Contributes to Embryonic Development and Tumor Suppression.","authors":"Priyanka Tibarewal, Laura Spinelli, Nisha Kriplani, Helen Wise, Nadege Poncet, Giulia Marzano, Karen E Anderson, Katarzyna M Grzes, Zofia Varyova, Mahreen Adil, C Peter Downes, Phillip T Hawkins, Len R Stephens, Kate G Storey, Doreen A Cantrell, Bart Vanhaesebroeck, Nicholas R Leslie","doi":"10.1111/cas.70476","DOIUrl":"10.1111/cas.70476","url":null,"abstract":"PTEN (phosphatase and tensin homolog deleted on chromosome ten) is a tumor suppressor, the function of which is impaired in many diverse cancers. It has phosphoinositide lipid phosphatase activity by which it suppresses activation of the oncogenic PI3K signaling network but in vitro also displays activity against protein substrates and is able to auto-dephosphorylate its Thr366 residue. Here we generate germline knock-in mice expressing PTEN-Y138L, a mutant enzyme which selectively lacks protein phosphatase activity and retains lipid phosphatase activity. Homozygous PtenY138L/Y138L mice die in utero before E10.5. Primary MEFs and thymocytes with only a single PtenY138L allele display normal low levels of AKT phosphorylation indicating effective regulation of PI3K signaling by endogenous PTEN-Y138L in vivo. Heterozygous Pten+/Y138L mice have reduced overall survival compared to wild-type littermates and develop tumors in multiple organs. Our data imply that in addition to its lipid phosphatase activity, the protein phosphatase activity of PTEN is also required for normal embryonic development and tumor suppression.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Pleiotropic Roles of FBXO11 in Tumorigenesis: Implications for Targeted Therapy. FBXO11在肿瘤发生中的多效性作用：靶向治疗的意义。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-07-17 DOI: 10.1111/cas.70483

Yuqi Zhang, Changyi Fan, Shiheng Chen, Tianyue Lu, Yuanyuan Li, Feng Du, Shanshan Wang

{"title":"Pleiotropic Roles of FBXO11 in Tumorigenesis: Implications for Targeted Therapy.","authors":"Yuqi Zhang, Changyi Fan, Shiheng Chen, Tianyue Lu, Yuanyuan Li, Feng Du, Shanshan Wang","doi":"10.1111/cas.70483","DOIUrl":"10.1111/cas.70483","url":null,"abstract":"F-box protein 11 (FBXO11), a critical component of the F-box protein family, serves as the substrate recognition subunit of the Skp1-Cul1-F-box (SCF) E3 ubiquitin ligase complex, orchestrates the ubiquitination and proteasomal degradation of a diverse array of substrates, thereby regulating various physiological and pathological processes. Emerging evidence reveals that FBXO11 is aberrantly expressed in multiple tumor types. Predominantly, FBXO11 functions as a potent tumor suppressor, and its downregulation is strongly correlated with tumor initiation, aggressive progression, and poor prognoses. Mechanistically, FBXO11 deficiency facilitates tumor development and metastasis by deregulating the cell cycle progression, enhancing cell migration and invasion, and driving epithelial-mesenchymal transition (EMT). However, the broad substrate spectrum of FBXO11 dictates its context-dependent roles in cancer biology, imparting significant challenges to its direct therapeutic targeting, as systemic modulation may yield unpredictable off-target or paradoxical effects. This review provides a comprehensive overview of current understanding of FBXO11 in oncology. By critically appraising its substrate diversity and functional versatility, we aim to re-evaluate the clinical translation of FBXO11, proposing that it be regarded not merely as a straightforward therapeutic target, but rather as a prognostic biomarker and a context-specific vulnerability that necessitates precision medicine strategies for effective clinical intervention.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Repression of ROBO1 Enhances Cisplatin Sensitivity in Hypermethylated Subtype of HPV-Positive Head and Neck Carcinoma. 抑制ROBO1增强hpv阳性头颈癌高甲基化亚型顺铂敏感性

IF 4.3 2区医学

Cancer Science Pub Date : 2026-07-16 DOI: 10.1111/cas.70482

Kenta Saeda, Takuya Nakagawa, Atsushi Okabe, Kazuko Kita, Tomoya Kurokawa, Masaki Fukuyo, Hiroki Ueda, Motoaki Seki, Bahityar Rahmutulla, Syuji Yonekura, Toyoyuki Hanazawa, Atsushi Kaneda

{"title":"Repression of ROBO1 Enhances Cisplatin Sensitivity in Hypermethylated Subtype of HPV-Positive Head and Neck Carcinoma.","authors":"Kenta Saeda, Takuya Nakagawa, Atsushi Okabe, Kazuko Kita, Tomoya Kurokawa, Masaki Fukuyo, Hiroki Ueda, Motoaki Seki, Bahityar Rahmutulla, Syuji Yonekura, Toyoyuki Hanazawa, Atsushi Kaneda","doi":"10.1111/cas.70482","DOIUrl":"10.1111/cas.70482","url":null,"abstract":"Although human papillomavirus-positive (HPV(+)) head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal squamous cell carcinoma (OPSCC), is generally associated with favorable outcomes, a subset of HPV(+) OPSCC remains resistant to chemoradiotherapy. We previously stratified clinical OPSCC cases using DNA methylome profiling and identified a significant correlation between elevated DNA methylation levels and favorable treatment response. To elucidate the molecular basis of this correlation, we performed integrated methylome analyses of 64 HPV(+) HNSCC cases in The Cancer Genome Atlas (TCGA) and 29 HPV(+) OPSCC cases in our Chiba cohort. We identified 595 genes showing significantly higher DNA methylation in good responders in each cohort. Additionally, using HNSCC cell lines, we extracted genes that exhibited both high DNA methylation and decreased expression in cisplatin (CDDP) sensitive cells. Twelve genes were consistently hypermethylated across both clinical cohorts, among which two genes, ROBO1 and SULT4A1, showed statistical significance and effect size. Functional validation demonstrated that ROBO1 knockdown in unmethylated HNSCC cells significantly suppressed cellular growth (p < 0.05), and additional exposure to CDDP further synergistically reduced cellular growth (p < 0.05). Conversely, ROBO1 overexpression conferred resistance to CDDP. CDDP resistance in unmethylated HNSCC cells led to upregulation of ROBO1 expression, suggesting an inverse relationship between ROBO1 silencing and drug resistance. Mechanistically, ROBO1 suppression increased DNA damage and apoptosis following CDDP treatment. These indicate that DNA hypermethylation of ROBO1 causally correlates with better treatment response of HPV(+) HNSCC, and its chemosensitivity might be enhanced by silencing of methylation target genes.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Proteomic Analysis Reveals AMPKα-Mediated Antiandrogen Resistance via Ferroptosis Suppression in Prostate Cancer. 蛋白质组学分析揭示ampk α通过抑制前列腺癌中铁下垂介导的抗雄激素抗性。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-07-13 DOI: 10.1111/cas.70477

Masaki Shiota, Tokiyoshi Tanegashima, Takahiko Hajime, Miho Ushijima, Shigehiro Tsukahara, Shohei Nagakawa, Satoshi Kobayashi, Takashi Matsumoto, Masatoshi Eto

{"title":"Proteomic Analysis Reveals AMPKα-Mediated Antiandrogen Resistance via Ferroptosis Suppression in Prostate Cancer.","authors":"Masaki Shiota, Tokiyoshi Tanegashima, Takahiko Hajime, Miho Ushijima, Shigehiro Tsukahara, Shohei Nagakawa, Satoshi Kobayashi, Takashi Matsumoto, Masatoshi Eto","doi":"10.1111/cas.70477","DOIUrl":"10.1111/cas.70477","url":null,"abstract":"Metastatic prostate cancer often develops resistance to second-generation androgen receptor pathway inhibitors (ARPIs) such as enzalutamide and darolutamide, limiting their long-term efficacy. In this study, we applied the high-precision absolute quantitative proteomics platform iMPAQT to comprehensively profile protein expression changes in multiple prostate cancer cell lines and their ARPI-resistant derivatives. Our analysis revealed consistent dysregulation of ferroptosis suppressor pathway alongside elevated phosphorylation of AMPKα signaling in resistant cells. While antiandrogen treatment increased lipid peroxidation in parental cells, resistant cells adapted by upregulating key ferroptosis-regulating proteins including FTH1 and GPX4, thereby evading ferroptosis. Functional assays demonstrated that the GPX4 inhibitor RSL3 selectively suppressed proliferation of resistant cells more potently than parental cells. Moreover, combination treatment with AMPKα inhibitors enhanced the anti-proliferative effect of RSL3. These findings suggest that ferroptosis suppression is a critical mechanism underpinning resistance to ARPIs in prostate cancer. Targeting pathways involved in ferroptosis regulation in combination with AMPKα inhibitors holds promise for overcoming therapeutic resistance and improving patient outcomes.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148438575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

AI-Based Analysis of Tumor-Infiltrating Lymphocytes and Homologous Recombination in Ovarian Cancer: JGOG3025-A1 Study. 基于人工智能的卵巢癌肿瘤浸润淋巴细胞及同源重组分析：JGOG3025-A1研究。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-07-10 DOI: 10.1111/cas.70474

Kohei Hamada, Junzo Hamanishi, Noriomi Matsumura, Akihiko Ueda, Shiro Takamatsu, Kosuke Yoshihara, Takayuki Nagasawa, Toshiyuki Seki, Akira Kikuchi, Etsuko Fujimoto, Mana Taki, Koji Yamanoi, Ryusuke Murakami, Hisaaki Kudo, Katsutoshi Oda, Muneaki Shimada, Aikou Okamoto, Masaki Mandai

{"title":"AI-Based Analysis of Tumor-Infiltrating Lymphocytes and Homologous Recombination in Ovarian Cancer: JGOG3025-A1 Study.","authors":"Kohei Hamada, Junzo Hamanishi, Noriomi Matsumura, Akihiko Ueda, Shiro Takamatsu, Kosuke Yoshihara, Takayuki Nagasawa, Toshiyuki Seki, Akira Kikuchi, Etsuko Fujimoto, Mana Taki, Koji Yamanoi, Ryusuke Murakami, Hisaaki Kudo, Katsutoshi Oda, Muneaki Shimada, Aikou Okamoto, Masaki Mandai","doi":"10.1111/cas.70474","DOIUrl":"10.1111/cas.70474","url":null,"abstract":"Understanding the tumor immune microenvironment, especially tumor-infiltrating lymphocytes (TILs), remains crucial in ovarian cancer. However, the distribution and prognostic significance of TILs across histological subtypes and genetic backgrounds remain unclear. As part of the JGOG3025-A1 study, diagnostic slides from 400 cases were collected. Two artificial intelligence-based cell classification models were used to evaluate the spatial distribution of TILs. The TIL score was calculated as the number of TILs divided by the analyzed area, and the immune-inflamed group was defined based on TIL scores. Among histological subtypes, high-grade serous carcinoma (HGSC) exhibited the highest TIL scores, clear cell carcinoma the lowest, and endometrioid carcinoma intermediate values. In HGSC, TIL scores did not significantly differ according to BRCA alteration or homologous recombination deficiency (HRD) status. The HRD/immune-inflamed group had the most favorable prognosis. In the homologous recombination-proficient population, the immune-inflamed group had better progression-free survival, whereas this trend did not appear for overall survival. In analyzes of the relationships between TIL levels and genomic structure, whole-genome doubling was associated with lower TIL infiltration in HRD tumors but showed no association in HRP tumors. In conclusion, HGSC showed the highest amount of TIL infiltration among subtypes, and prognostic stratification can be achieved by integrating pathology-based immunophenotypes and HRD status.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148425766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

YBX1 Promotes Malignant Progression of HNSCC via Stabilizing NSUN2-m5C Modified ATF4 mRNA. YBX1通过稳定NSUN2-m5C修饰的ATF4 mRNA促进HNSCC恶性进展。

IF 4.3 2区医学

Cancer Science Pub Date : 2026-07-10 DOI: 10.1111/cas.70467

Yanwei Li, Shuang Li, Yang Li, Zhanyu Pan

{"title":"YBX1 Promotes Malignant Progression of HNSCC via Stabilizing NSUN2-m5C Modified ATF4 mRNA.","authors":"Yanwei Li, Shuang Li, Yang Li, Zhanyu Pan","doi":"10.1111/cas.70467","DOIUrl":"10.1111/cas.70467","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) remains a major therapeutic challenge because of its aggressive metastatic behavior and the paucity of effective targeted therapies. The present study identifies YBX1 as a critical 5-methylcytosine (m5C) reader that cooperates with the m5C methyltransferase NSUN2 to promote malignant progression through mRNA stabilization. Integrated analysis of The Cancer Genome Atlas datasets demonstrated significant upregulation of YBX1 in HNSCC. Clinical validation in a cohort of 77 patients further showed that elevated YBX1 expression was a significant risk factor for poor overall survival, with a hazard ratio of 1.184. Functional analyses in vitro and in vivo revealed that YBX1 depletion markedly suppressed proliferation, migration, and invasion, whereas YBX1 overexpression enhanced these oncogenic properties in multiple HNSCC cell lines and xenograft models. Mechanistic investigations using m5C methylated RNA immunoprecipitation sequencing (m5C-MeRIP-seq) combined with YBX1-RIP-seq identified ATF4 mRNA as a direct YBX1 target containing m5C modifications within its coding region. NSUN2-dependent m5C deposition significantly increased YBX1 binding affinity, thereby stabilizing ATF4 transcripts (p < 0.001). Luciferase reporter assays confirmed the specificity of YBX1 recognition of m5C-modified ATF4 mRNA. Collectively, these findings define an epitranscriptomic regulatory pathway in which YBX1 decodes NSUN2-installed m5C marks to enhance oncogenic mRNA stability and support tumor progression. Dual inhibition of YBX1 and NSUN2 is therefore proposed as a potential therapeutic strategy for HNSCC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148425715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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