British Journal of Cancer最新文献_第8页

A functional landscape for chromosome 17q in neuroblastoma: balancing replication stress and genomic stability. 神经母细胞瘤中染色体17q的功能景观：平衡复制压力和基因组稳定性。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-08-07 DOI: 10.1038/s41416-026-03569-w

Elien Hilgert, Lisa Depestel, Nadine Van Roy, Stephen Roberts, Kaat Durinck, Frank Speleman

{"title":"A functional landscape for chromosome 17q in neuroblastoma: balancing replication stress and genomic stability.","authors":"Elien Hilgert, Lisa Depestel, Nadine Van Roy, Stephen Roberts, Kaat Durinck, Frank Speleman","doi":"10.1038/s41416-026-03569-w","DOIUrl":"https://doi.org/10.1038/s41416-026-03569-w","url":null,"abstract":"<p><p>Neuroblastoma is characterised by extensive genomic instability despite a marked paucity of recurrent somatic mutations. Instead, the disease is predominantly driven by chromosomal alterations, including segmental chromosomal imbalances, small structural variants, and oncogene amplification. A major unmet challenge is identifying key oncogenic drivers, beyond MYCN amplification, hidden within these recurrent DNA copy number alterations. Extra wild-type gene copies can alter expression levels and thus contribute to tumour development and affect survival. Increasing evidence suggests that these copy number-affected genes confer resistance to replication stress, a hallmark of high-risk neuroblastoma tumours. Among the most frequent and prognostically significant alterations is the gain of chromosome 17q. In this review, we discuss selected top-ranked candidate genes on 17q implicated in replication fork dynamics and DNA damage repair that we previously identified through an integrative functional genomics study. Improved understanding of the mechanisms by which 17q copy number-driven genes regulate replication stress responses and DNA damage repair may expose fundamental vulnerabilities in aggressive neuroblastoma and guide the development of novel targeted therapeutic strategies.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688574","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}

引用次数: 0

In-depth characterisation of the tumour microenvironment reveals HHV-8-dependent immune regulation in HIV-associated and classic Kaposi sarcoma 深入表征肿瘤微环境揭示hhv -8依赖性免疫调节在hiv相关和经典的卡波西肉瘤。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-08-05 DOI: 10.1038/s41416-026-03536-5

Claudia A. M. Fulgenzi, Alessia Dalla Pria, Yiran Zhao, Alberto Giovanni Leone, Justin Weir, Ignazio Puccio, Krista S. Tuohinto, Päivi M. Ojala, Mark Bower, David J. Pinato

{"title":"In-depth characterisation of the tumour microenvironment reveals HHV-8-dependent immune regulation in HIV-associated and classic Kaposi sarcoma","authors":"Claudia A. M. Fulgenzi, Alessia Dalla Pria, Yiran Zhao, Alberto Giovanni Leone, Justin Weir, Ignazio Puccio, Krista S. Tuohinto, Päivi M. Ojala, Mark Bower, David J. Pinato","doi":"10.1038/s41416-026-03536-5","DOIUrl":"10.1038/s41416-026-03536-5","url":null,"abstract":"Kaposi’s sarcoma (KS) is the most common malignancy occurring in people living with HIV (PLWH). The clinical course of KS in PLWH established on combined anti-retroviral therapy (cART) resembles that of classic KS. To compare the clinical and biological characteristics of HIV-associated KS in patients with well-controlled viral infection (N = 21) and non-HIV-associated KS (N = 19). Clinical data were prospectively collected from patients treated at the National Centre for HIV malignancies at Chelsea & Westminster Hospital. Targeted transcriptomic analysis and multiplex immune-fluorescence were performed on archival tumour samples. Clinical outcomes were comparable between groups. The tumour microenvironment (TME) of non-HIV-associated KS was characterised by transcriptional upregulation of pathways associated with adaptive and innate immunity and angiogenesis. The TME of HIV-associated cases was associated with lower infiltration of activated CD4 cells. In both cohorts, we found the expression of HHV-8 genes to positively correlate with activated CD4, CD8, NK and immune checkpoint gene expression. The KS TME in the presence of well-controlled HIV infection is characterised by a lower degree of inflammation and more pronounced epithelial to mesenchymal transition. We also identified intra-tumoral HHV-8 gene expression as a driver of TME composition.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1544-1553"},"PeriodicalIF":7.8,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03536-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673030","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 Phase 1/2 study of ontorpacept (TTI-621) in combination with doxorubicin in patients with unresectable or metastatic high-grade leiomyosarcoma 一项1/2期研究：奥托帕普（TTI-621）联合阿霉素治疗不可切除或转移性高级别平滑肌肉瘤。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-08-04 DOI: 10.1038/s41416-026-03574-z

Sujana Movva, Victoria Allgood, Rashmi Chugh, Lara E. Davis, Howard H. Bailey, Mohammed Milhem, Varun Monga, Steven Attia, Ankit Mangla, Ingmar Bruns, Luke Kuttschreuter, Dalila Bouyoucef-Cherchalli, Caimiao Wei, Gloria H. Y. Lin, Hong Zhang, Ilan Pomerance, Mihaela Druta, Sant Chawla

{"title":"A Phase 1/2 study of ontorpacept (TTI-621) in combination with doxorubicin in patients with unresectable or metastatic high-grade leiomyosarcoma","authors":"Sujana Movva, Victoria Allgood, Rashmi Chugh, Lara E. Davis, Howard H. Bailey, Mohammed Milhem, Varun Monga, Steven Attia, Ankit Mangla, Ingmar Bruns, Luke Kuttschreuter, Dalila Bouyoucef-Cherchalli, Caimiao Wei, Gloria H. Y. Lin, Hong Zhang, Ilan Pomerance, Mihaela Druta, Sant Chawla","doi":"10.1038/s41416-026-03574-z","DOIUrl":"10.1038/s41416-026-03574-z","url":null,"abstract":"Ontorpacept, a recombinant signal regulatory protein alpha (SIRPα)–blocking fusion protein, has antitumour activity by disrupting CD47–SIRPα signalling. This Phase 1/2 study examined ontorpacept with doxorubicin in patients with leiomyosarcoma. Eligible patients were ≥18 years with metastatic or locally advanced high-grade soft-tissue sarcomas (high-grade leiomyosarcoma in Phase 2). In Phase 1, patients received escalating doses of ontorpacept plus doxorubicin. Phase 2 dose expansion evaluated ontorpacept doses 0.2, 1.0, and 2.0 mg/kg plus doxorubicin. The primary endpoints were safety (Phase 1); and objective response rate (ORR) (Phase 1/2). Seventy-six patients were enrolled (Phase 1, n = 9; Phase 2, n = 67). No dose-limiting toxicities occurred in Phase 1. The most common treatment-related adverse events were neutrophil count decreased/neutropenia (grade ≥3 in 66% of patients). In Phase 1, one patient receiving ontorpacept 2.0 mg/kg had a confirmed partial response. In Phase 2, six patients receiving ontorpacept 0.2 mg/kg (ORR, 18.8%; 95% CI, 7.2–36.4) and one patient receiving 2.0 mg/kg (ORR, 4.5%; 95% CI, 0.1–22.8) had confirmed partial responses. This first study of CD47 inhibition with chemotherapy in leiomyosarcomas shows manageable safety, supporting further investigation of ontorpacept dosing and schedule, in combination with doxorubicin and as monotherapy.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1439-1451"},"PeriodicalIF":7.8,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03574-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672932","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

Comparison of NICE criteria with the BOADICEA multifactorial risk model to guide breast cancer risk assessment and referral amongst women under age 50 within primary care NICE标准与BOADICEA多因素风险模型的比较，以指导50岁以下妇女在初级保健中的乳腺癌风险评估和转诊

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-08-04 DOI: 10.1038/s41416-026-03547-2

Reuben Frost, Lorenzo Ficorella, Amy Berrington de Gonzalez, Antonis C. Antoniou, Montserrat García-Closas, Juliet A. Usher-Smith

{"title":"Comparison of NICE criteria with the BOADICEA multifactorial risk model to guide breast cancer risk assessment and referral amongst women under age 50 within primary care","authors":"Reuben Frost, Lorenzo Ficorella, Amy Berrington de Gonzalez, Antonis C. Antoniou, Montserrat García-Closas, Juliet A. Usher-Smith","doi":"10.1038/s41416-026-03547-2","DOIUrl":"10.1038/s41416-026-03547-2","url":null,"abstract":"The National Institute for Health and Care Excellence (NICE) recommends that women at above-population-level risk of breast cancer (BC) are offered enhanced screening and risk-reducing interventions. Identification of these women largely relies on referral through primary care based on family history criteria. We compared the performance of the NICE criteria with versions of the BOADICEA multifactorial risk model in identifying women who developed BC within 10 years. Analyses included 1258 women aged under 50 years with family history, reproductive, lifestyle and polygenic risk data recruited to the Generations Study between 2004 and 2011 (392 BC cases), weighted to represent the UK population with respect to age and family history of BC. NICE criteria identified 4.4% of women who developed BC within 10 years amongst 1.4% of women who met referral criteria. The full BOADICEA model identified up to 35% of women who developed BC, but with lower specificity and 26.5% of women meeting referral criteria. NICE family history-based criteria applied to women under 50 miss most BCs occurring within 10 years. Multifactorial risk assessment in primary care could substantially improve the identification of women at risk who could be offered interventions before being invited to population-based screening.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1452-1462"},"PeriodicalIF":7.8,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03547-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668444","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

AKR1B10 as a serum marker for diagnosis and postoperative monitoring of hepatocellular carcinoma AKR1B10作为肝细胞癌诊断和术后监测的血清标志物。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-08-04 DOI: 10.1038/s41416-026-03530-x

Ming Xie, Xu Ye, Qi Yu, Wentao Tang, Yuting Ou, Miaozhi Gao, Baoluhe Zhang, Bin Wu, Zhe Cao, Xi Zeng, Shunda Du, Deliang Cao

{"title":"AKR1B10 as a serum marker for diagnosis and postoperative monitoring of hepatocellular carcinoma","authors":"Ming Xie, Xu Ye, Qi Yu, Wentao Tang, Yuting Ou, Miaozhi Gao, Baoluhe Zhang, Bin Wu, Zhe Cao, Xi Zeng, Shunda Du, Deliang Cao","doi":"10.1038/s41416-026-03530-x","DOIUrl":"10.1038/s41416-026-03530-x","url":null,"abstract":"Aldo-keto reductase 1B10 (AKR1B10) is a novel serum marker for hepatocellular carcinoma (HCC). This study was aimed to evaluate its clinical value in the diagnosis and immediate postoperative monitoring for HCC. A total of 1197 subjects were recruited from two study centers, including 185 patients with HCC who underwent radical resection and followed up for 3 months. Serum samples were collected from all participants for AKR1B10 and alpha-fetoprotein (AFP) tests, and imaging and clinical data were collected. Serum AKR1B10 in HCC patients markedly increased to 1384.31 ± 107.91 pg/ml. Receiver operating characteristic (ROC) curve analysis showed an area under curve (AUC) of 0.877, sensitivity of 71.2%, and specificity of 97.2% for AKR1B10 in HCC compared to 0.792, 62.7%, and 88.7% for AFP. For early HCC, serum AKR1B10 had an AUC of 0.855, sensitivity of 70.6%, and specificity of 94.4% compared to 0.744, 56.7%, and 86.7% for AFP. After radical resection of HCC, serum AKR1B10 rapidly decreased to the normal range within 3-5 days whereas AFP remained high. At 1-3 months after surgery, serum AKR1B10 was consistent with imaging data in 89.11% of patients with HCC, whereas AFP had only 70.41%. AKR1B10 is an effective serum marker for diagnosis of HCC and postoperative monitoring of HCC, with better clinical performance than AFP.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1535-1543"},"PeriodicalIF":7.8,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672891","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}

引用次数: 0

Priorities for breast cancer risk assessment in UK women under age 50: a survey and discrete choice experiment 英国50岁以下女性乳腺癌风险评估的优先级：一项调查和离散选择实验。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-08-04 DOI: 10.1038/s41416-026-03546-3

Rebecca A. Dennison, Maria Valasaki, Stuart Wright, Reuben Frost, Sacha J. Howell, Antonis C. Antoniou, Douglas F. Easton, Stephen Morris, Montserrat Garcia-Closas, Victoria G. Woof, David P. French, Juliet A. Usher-Smith

{"title":"Priorities for breast cancer risk assessment in UK women under age 50: a survey and discrete choice experiment","authors":"Rebecca A. Dennison, Maria Valasaki, Stuart Wright, Reuben Frost, Sacha J. Howell, Antonis C. Antoniou, Douglas F. Easton, Stephen Morris, Montserrat Garcia-Closas, Victoria G. Woof, David P. French, Juliet A. Usher-Smith","doi":"10.1038/s41416-026-03546-3","DOIUrl":"10.1038/s41416-026-03546-3","url":null,"abstract":"National guidelines recommend English women between 30 and 49 years with moderate/high risk of breast cancer (BC) be offered screening and prevention interventions. Identification  largely relies on family history-based criteria amongst women self-presenting in primary care. We aimed to understand the preference for different potential risk assessment strategies in this population. A cross-sectional survey including a discrete choice experiment. Risk assessments were defined using six attributes, including initiation strategy, eligibility for a full/detailed risk assessment, components of the risk assessment, including multifactorial risk assessment based on the BOADICEA/CanRisk model, and sensitivity. Coefficients from conditional logistic regression were used to estimate preference for different risk assessment approaches compared to current care. Participants (n = 893) preferred alternative approaches for risk assessments over current care, particularly where all eligible women were proactively invited and more above-average risk women were correctly identified. All but one of 21 risk assessment approaches was preferred, with the most favoured approaches having a probability of being preferred over current care >92%. Education level and ethnicity potentially impacted the strength of participant priorities. Offering multifactorial BC risk assessments to younger women in primary care, especially the most proactive and broad approaches, would be acceptable and preferred over current practice.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1430-1438"},"PeriodicalIF":7.8,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03546-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668447","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

Identification of microRNAs as biomarkers for triage of cervical intraepithelial neoplasia in cervical scrape samples from high-risk HPV-positive women 鉴定microrna作为鉴别高危hpv阳性妇女宫颈刮擦标本中宫颈上皮内瘤变的生物标志物。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-08-04 DOI: 10.1038/s41416-026-03521-y

Lidy Vannessa Mejia Guarnizo, Clara Esperanza Trujillo Gama, Liliana López kleine, Carlos Alberto Orozco Castaño, Sebastián Prada Padilla, Josefa Antonia Rodríguez García, María Mercedes Bravo Hernandez

{"title":"Identification of microRNAs as biomarkers for triage of cervical intraepithelial neoplasia in cervical scrape samples from high-risk HPV-positive women","authors":"Lidy Vannessa Mejia Guarnizo, Clara Esperanza Trujillo Gama, Liliana López kleine, Carlos Alberto Orozco Castaño, Sebastián Prada Padilla, Josefa Antonia Rodríguez García, María Mercedes Bravo Hernandez","doi":"10.1038/s41416-026-03521-y","DOIUrl":"10.1038/s41416-026-03521-y","url":null,"abstract":"Cervical cancer (CC) is the fourth leading cause of cancer death in women worldwide. High-risk human papillomavirus (HR-HPV) testing is highly sensitive but lacks specificity for identifying women at risk of progression. Reliable biomarkers are urgently needed to identify HR-HPV-positive women most likely to develop cervical cancer. Aberrant microRNA (miRNA) expression contributes to HPV-driven carcinogenesis and represents a promising diagnostic tool. Cervical scrape samples from HR-HPV-positive women were histologically classified as low-grade (≤CIN1) or high-grade (CIN2/3). Total RNA was extracted and small RNA sequencing performed to identify differentially expressed miRNAs. Bioinformatic analyses included clustering, ROC curves, logistic regression, and functional enrichment. Selected candidates were validated byRT-qPCR in independent samples. Nineteen dysregulated miRNAs distinguished low- from high-grade lesions, six linked to viral and cancer pathways. Three (hsa-miR-501-3p, hsa-miR-1271-5p, hsa-miR-9-5p) were validated by RT-qPCR and showed strong discriminatory capacity. hsa-miR-501-3p reached high diagnostic accuracy (AUC = 0.88), which improved to 0.94 when combined with the others. The validated signature achieved high sensitivity and specificity for detecting high-grade lesions. This pioneering study in Colombia using cervical scrapes demonstrates that miRNAs are potential biomarkers for high-grade cervical lesions and that this clinically relevant, minimally invasive sample routinely collected in screening supports their use.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1524-1534"},"PeriodicalIF":7.8,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03521-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673068","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

Super-enhancer landscape regulated by CDK12 drives retinoblastoma progression CDK12调控的超增强子景观驱动视网膜母细胞瘤进展。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-08-03 DOI: 10.1038/s41416-026-03563-2

Caiyao Guo, Wei Dai, Jingxuan Li, Xuan Zhou, Jianqiong Yang, Fenfen Xie, Wan Liang, Jingfeng Zhou, Wen Hou, Jinxia Lan, Hai Liu, Shenglan Liu

{"title":"Super-enhancer landscape regulated by CDK12 drives retinoblastoma progression","authors":"Caiyao Guo, Wei Dai, Jingxuan Li, Xuan Zhou, Jianqiong Yang, Fenfen Xie, Wan Liang, Jingfeng Zhou, Wen Hou, Jinxia Lan, Hai Liu, Shenglan Liu","doi":"10.1038/s41416-026-03563-2","DOIUrl":"10.1038/s41416-026-03563-2","url":null,"abstract":"Retinoblastoma (RB) lacks effective targeted therapies. Super-enhancers (SEs) are crucial for tumorigenesis, yet their role in RB was unclear. We profiled active SEs in RB cells using chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq). qRT-PCR, single-cell RNA sequencing (scRNA-Seq) and immunohistochemistry (IHC) were employed to identify the critical regulator of SE activity. The anti-tumour effect of targeted blockade of SE regulator, achieved via pharmacological degradation and specific lentiviruses, was investigated in vitro and in preclinical models of subcutaneous, intraocular, and central nervous system (CNS)-metastatic RB. Cyclin-dependent kinase 12 (CDK12) was identified as a key SE regulator. SE-driven oncogenic transcription was suppressed by CDK12 inhibition, leading to eliminated tumour outgrowth and metastasis. In addition, SE-associated oncogenes BIRC5 and PTPRC were identified as essential for RB cell survival and stemness. Furthermore, PTPRC overexpression rescued the anti-tumour effect of BSJ-4-116. This study defines CDK12 as a master regulator of oncogenic SEs in RB. Targeting the CDK12-SE axis, via CDK12 or downstream effectors like BIRC5/PTPRC, presents a novel therapeutic strategy.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1402-1416"},"PeriodicalIF":7.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03563-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668517","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

Spatial proteomics deciphers the immune niche landscape of non-ampullary duodenal adenocarcinoma 空间蛋白质组学解读非壶腹十二指肠腺癌的免疫生态位景观。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-07-31 DOI: 10.1038/s41416-026-03568-x

Yuichiro Kohara, Satoshi Yasuda, Tomoko Uchiyama, Minako Nagai, Kota Nakamura, Yasuko Matsuo, Takanari Tatsumi, Taichi Terai, Shunsuke Doi, Takeshi Sakata, Yuki Osamura, Sotaro Matsuhisa, Akihiko Yoshizawa, Yutaka Suzuki, Masayuki Sho

{"title":"Spatial proteomics deciphers the immune niche landscape of non-ampullary duodenal adenocarcinoma","authors":"Yuichiro Kohara, Satoshi Yasuda, Tomoko Uchiyama, Minako Nagai, Kota Nakamura, Yasuko Matsuo, Takanari Tatsumi, Taichi Terai, Shunsuke Doi, Takeshi Sakata, Yuki Osamura, Sotaro Matsuhisa, Akihiko Yoshizawa, Yutaka Suzuki, Masayuki Sho","doi":"10.1038/s41416-026-03568-x","DOIUrl":"10.1038/s41416-026-03568-x","url":null,"abstract":"Non-ampullary duodenal adenocarcinoma (NADA) is a rare malignancy with an incompletely characterised tumour immune microenvironment (TME). We aimed to elucidate its immune niche landscape and validate a clinically applicable transcriptomic surrogate. In 38 resected NADA cases, multiplex immunofluorescence spatial proteomics was performed on tissue microarrays, validated by cohort-wide whole-slide imaging. A 10-gene qRT-PCR panel capturing adaptive immune resistance mechanisms was integrated with spatial data. Molecular microsatellite instability (MSI) testing confirmed mismatch repair (MMR) status in all integrated cases. Spatial proteomics identified seven distinct cellular niches; the immune-active “Hot spot” niche showed a trend toward prolonged survival. The 10-gene panel classified patients into “Hot,” “Intermediate,” and “Cold” clusters, with the “Hot” cluster significantly enriched in “Hot spot.” A pMMR subgroup with abundant “Hot spot” (7/29, 24.1%) was identified, most belonging to the “Hot” cluster (5/7, 71.4%). Molecular MSI testing confirmed all pMMR “Hot” cases as microsatellite stable. External transcriptomic analysis revealed enrichment of interferon-gamma and inflammatory response pathways in the “Hot” group. Spatial proteomics identified an immune-active “Hot spot” niche in NADA. The 10-gene panel serves as a spatial surrogate, identifying a microsatellite-stable pMMR subgroup that may represent a biologically relevant subgroup for future investigation.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1512-1523"},"PeriodicalIF":7.8,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648405","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}

引用次数: 0

Age- and sex-dependent associations of metabolic syndrome with colorectal cancer in the UK Biobank 英国生物银行中代谢综合征与结直肠癌的年龄和性别依赖性关联。

IF 7.8 1区医学

British Journal of Cancer Pub Date : 2026-07-30 DOI: 10.1038/s41416-026-03564-1

Zilin Luo, Fatemeh Safizadeh, Marko Mandic, Michael Hoffmeister, Hermann Brenner

{"title":"Age- and sex-dependent associations of metabolic syndrome with colorectal cancer in the UK Biobank","authors":"Zilin Luo, Fatemeh Safizadeh, Marko Mandic, Michael Hoffmeister, Hermann Brenner","doi":"10.1038/s41416-026-03564-1","DOIUrl":"10.1038/s41416-026-03564-1","url":null,"abstract":"The concurrent rise in metabolic syndrome (MetS) and the changing age profile of colorectal cancer (CRC) necessitates clarifying the heterogeneity in their association across demographic groups. This study aimed to define the precise age- and sex-specific associations between MetS and CRC risk, addressing a key gap to inform targeted prevention paradigms. In this cohort study, we analysed data from UK Biobank participants aged 40–69 years (recruited 2006–2010). Participants were stratified by age (<60 or ≥60 years) and sex into four groups. Multivariable Cox proportional hazards models were used to assess the associations of MetS, the number of metabolic abnormalities, and each component with CRC incidence. Among 379,173 participants, 4971 developed CRC during a median follow-up of 11.8 years. MetS was most strongly associated with CRC in younger males (hazard ratio [HR] 1.31, 95% CI 1.15–1.50), significantly in older adults of both males (HR 1.18, 95% CI 1.07–1.30) and females (HR 1.18, 95% CI 1.05–1.33), but not in younger females (HR 1.05, 95% CI 0.89–1.25). Older males but not females showed increasing risks when having 3, 4, and 5 abnormalities compared to none, respectively. Beyond younger females, elevated waist circumference was the sole component consistently linked to higher risk. The association between MetS and CRC is strongly dependent on age and sex in White populations, with the highest risk concentrated in young and middle-aged males. These findings directly support risk-stratified prevention and provide crucial clues for investigating the underlying sex- and age-specific biological mechanisms.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"135 9","pages":"1463-1469"},"PeriodicalIF":7.8,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41416-026-03564-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629387","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}

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