British Journal of Cancer最新文献

Integrated multi-omics and single-cell analyses identify metabolic heterogeneity and therapeutic vulnerabilities in medullary thyroid cancer. 综合多组学和单细胞分析鉴定甲状腺髓样癌的代谢异质性和治疗脆弱性。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-05-07 DOI: 10.1038/s41416-026-03467-1

Chuqiao Liu, Cenkai Shen, Yingtong Hou, Yuxin Du, Yihao Liu, Danni Liu, Yan Zhang, Xiaoqi Mao, Yujian Song, Zimeng Li, Qinghai Ji, Xiao Shi, Yu Wang, Wenjun Wei

{"title":"Integrated multi-omics and single-cell analyses identify metabolic heterogeneity and therapeutic vulnerabilities in medullary thyroid cancer.","authors":"Chuqiao Liu, Cenkai Shen, Yingtong Hou, Yuxin Du, Yihao Liu, Danni Liu, Yan Zhang, Xiaoqi Mao, Yujian Song, Zimeng Li, Qinghai Ji, Xiao Shi, Yu Wang, Wenjun Wei","doi":"10.1038/s41416-026-03467-1","DOIUrl":"https://doi.org/10.1038/s41416-026-03467-1","url":null,"abstract":"Background: Medullary thyroid cancer (MTC) is a heterogeneous and aggressive malignancy with limited therapeutic options. Metabolic reprogramming, a hallmark of cancer, may offer a promising avenue for understanding and managing MTC.Methods: RNA sequencing data of 101 MTC samples were obtained from a published dataset PRJCA008783, and untargeted metabolomic profiling was performed on 51 paired samples. Metabolic subtypes were identified using clustering analyses and validated using immunohistochemistry (47 cases), multiplex immunofluorescence (12 cases), and a previously published single-cell RNA sequencing dataset (7 cases derived from PRJCA021386). Deep learning-based approaches were applied to develop prognostic models.Results: Three metabolic subtypes were identified. The M3 subtype, associated with poor prognosis, was characterised by upregulated glycosaminoglycan (GAGs) biosynthesis, particularly chondroitin sulfate, and elevated expression of CHSY1, a key GAGs biosynthetic enzyme. M3 tumours displayed enhanced epithelial-mesenchymal transition (EMT) signatures. Multi-omic analyses implicated CHSY1 may promote EMT through interactions with myofibroblasts, which was supported by immunohistochemistry and immunofluorescence. Two prognostic classifiers, the 8 Metabolites Model and the 28 Metabolic Genes Model, effectively stratified patients by recurrence risk, with predictive power largely driven by GAGs-associated metabolism.Conclusions: Our study reveals substantial metabolic heterogeneity in MTC and proposes a novel metabolic classification system, offering mechanistic insights and supporting metabolite-driven prognostication for precision management of MTC.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833726","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

Runx1 and Runx2 act in concert to suppress Wnt/β-catenin-driven mammary tumourigenesis. Runx1和Runx2协同抑制Wnt/β-连环蛋白驱动的乳腺肿瘤发生。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-05-07 DOI: 10.1038/s41416-026-03439-5

Alessandra I Riggio, Kerri Sweeney, Robin Shaw, Amy Lawlor, Adiba Khan, Nicola Ferrari, Jayanthi Anand, Laura Ca Galbraith, Kathryn Gilroy, Courtney Bull, Alex L Young, Dimitris Athineos, Holly Hall, Farah Ghaffar, Mark Hughes, Claire A Mitchell, Louise Mitchell, Colin Nixon, Peter D Adams, Edward W Roberts, Crispin J Miller, Philip D Dunne, Kirsteen J Campbell, Ewan R Cameron, Karen Blyth

{"title":"Runx1 and Runx2 act in concert to suppress Wnt/β-catenin-driven mammary tumourigenesis.","authors":"Alessandra I Riggio, Kerri Sweeney, Robin Shaw, Amy Lawlor, Adiba Khan, Nicola Ferrari, Jayanthi Anand, Laura Ca Galbraith, Kathryn Gilroy, Courtney Bull, Alex L Young, Dimitris Athineos, Holly Hall, Farah Ghaffar, Mark Hughes, Claire A Mitchell, Louise Mitchell, Colin Nixon, Peter D Adams, Edward W Roberts, Crispin J Miller, Philip D Dunne, Kirsteen J Campbell, Ewan R Cameron, Karen Blyth","doi":"10.1038/s41416-026-03439-5","DOIUrl":"https://doi.org/10.1038/s41416-026-03439-5","url":null,"abstract":"Introduction: The genes encoding RUNX1 and its binding partner CBFβ are recurrently reported to be mutated in breast cancer, a major cause of mortality in women worldwide. However, the functional role for these proteins remains unproven.Methods: The putative tumour suppressor role of Runx1 was investigated in genetic mouse models of breast cancer. Stem cell assays, immunohistochemistry and RNAseq analyses were applied to study biological and molecular mechanisms.Results: Runx1 loss of function leads to accelerated disease onset and tumour development in breast cancer models. Combined deletion of Runx1 and Runx2 further resulted in mammary cells becoming exquisitely sensitive to WNT-driven transformation, with expedited emergence of multiple tumours. Runx1 ablation induces a stem cell-like phenotype in mammary epithelial cells, whilst transcriptomic analysis demonstrated activation of multiple oncogenic pathways, especially when Runx2 was co-deleted. Altered Runx expression in the mammary epithelium also drove alterations in the tumour immune microenvironment, with changes to neutrophil and macrophage populations.Conclusions: Runx1 restricts some forms of breast cancer and inhibits the full oncogenic potential of aberrant WNT signalling. Combined Runx1 and Runx2 loss dramatically accelerates disease progression suggesting that Runx2 can substitute for Runx1 in dampening the oncogenic effects of WNT signalling.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833737","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

Targeting NUDT21-mediated alternative polyadenylation of oncogenes ameliorates colorectal cancer malignancy and metastasis. 靶向nudt21介导的癌基因选择性多腺苷化可改善结直肠癌的恶性和转移。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-05-06 DOI: 10.1038/s41416-026-03451-9

Shih-Chieh Lin, Ya-Chuan Tsai, Jui-Lin Wang, Hsian-Jean Chin, Ching-Chin Tsai, Shin-Chih Lin, Yi-Syuan Lin, Bo-Wen Lin, Shaw-Jenq Tsai

{"title":"Targeting NUDT21-mediated alternative polyadenylation of oncogenes ameliorates colorectal cancer malignancy and metastasis.","authors":"Shih-Chieh Lin, Ya-Chuan Tsai, Jui-Lin Wang, Hsian-Jean Chin, Ching-Chin Tsai, Shin-Chih Lin, Yi-Syuan Lin, Bo-Wen Lin, Shaw-Jenq Tsai","doi":"10.1038/s41416-026-03451-9","DOIUrl":"https://doi.org/10.1038/s41416-026-03451-9","url":null,"abstract":"Background: Colorectal cancer (CRC) is a disease leading cause of death worldwide. Lacking molecular markers for early detection and suitable candidates for targeted therapies are two main reasons for causing CRC malignancy.Objectives: Exploring the role of NUDT21 in colorectal cancer metastasis.Methods: A systematic bioinformatic analysis identified key genes involved in colorectal cancer, which were subsequently validated through loss-of-function and gain-of-function experiments conducted both in vitro and in vivo.Results: Overexpression of nucleoside diphosphate linked moiety X hydrolases-type motif 21 (NUDT21), a critical factor that regulates alternative polyadenylation, is observed in malignant polyps and in human and mouse CRC. Survival analysis reveals that high level of NUDT21 is associated with poor prognosis. NUDT21 knockdown not only inhibits cell growth but also reduces malignancy traits like anchorage-independent growth and cancer stemness. RNA-seq and RIP-seq results show NUDT21 preferentially binds to the proximal alternative polyadenylation site of numerous oncogenes to promote their expression and thus drive the progression of CRC. Treatment with re-purposing drugs targeting NUDT21 exhibit therapeutic potential in cell culture, organoid, orthotopic, and patient-derived xenografted CRC models.Conclusions: These findings demonstrate that NUDT21 is a critical regulator of colon cancer progression and a promising therapeutic target for CRC.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833712","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

JPI-547, a novel dual inhibitor of PARP1/2 and tankyrase is more effective than first-generation PARP inhibitors in preclinical BRCA1/2-mutated cancer models. JPI-547是一种新的PARP1/2和tankyrase双抑制剂，在临床前brca1 /2突变的癌症模型中比第一代PARP抑制剂更有效。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-05-06 DOI: 10.1038/s41416-026-03411-3

Min Sil Kang, Nar Bahadur Katuwal, Mithun Ghosh, Sa Deok Hong, Yeong Gyu Jeong, Seong Min Park, Tae Hoen Kim, Seul-Gi Kim, Seung Ryeol Lee, Yong Wha Moon

{"title":"JPI-547, a novel dual inhibitor of PARP1/2 and tankyrase is more effective than first-generation PARP inhibitors in preclinical BRCA1/2-mutated cancer models.","authors":"Min Sil Kang, Nar Bahadur Katuwal, Mithun Ghosh, Sa Deok Hong, Yeong Gyu Jeong, Seong Min Park, Tae Hoen Kim, Seul-Gi Kim, Seung Ryeol Lee, Yong Wha Moon","doi":"10.1038/s41416-026-03411-3","DOIUrl":"https://doi.org/10.1038/s41416-026-03411-3","url":null,"abstract":"Background: Poly(ADP-ribose) polymerase (PARP) inhibitors are highly effective therapies for BRCA1/2-mutated tumors. However, most patients eventually develop acquired resistance. Here, we report that JPI-547, a second-generation PARP inhibitor targeting both PARP1/2 and tankyrase, demonstrates potent antitumor activity in olaparib-sensitive and resistant BRCA1/2 mutant models.Methods: Olaparib-resistant (OR) models were generated using BRCA-mutated human ovarian and breast cancer cell lines and ovarian Patient-Derived Tumor Xenograft (PDTX) by exposing to olaparib. For clinical relevance, public mRNA microarray datasets of ovarian and breast cancer were analyzed.Results: JPI-547 demonstrated better antitumor efficacy in both olaparib-sensitive and resistant BRCA-mutated preclinical models than first-generation PARP inhibitors. Mechanistically, the on-target inhibition of PARP1/2 and tankyrase by JPI-547 strongly inhibited the restoration of homologous recombination (HR) activity by suppressing RAD51 expression. This action resulted in the retardation of tumor growth in olaparib-sensitive and resistant ovarian PDTX models. Furthermore, high RAD51 expression was significantly associated with poor prognosis in ovarian and breast cancer patients based on public mRNA expression data.Conclusion: These results suggest the scientific rationale for further clinical development of JPI-547 for treating both PARP inhibitor-sensitive patients and those resistant to first-generation PARP inhibitors in BRCA-mutated cancers.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833660","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

The association between hospital frailty risk score and adverse inpatient outcomes in older adults with colorectal cancer. 老年结直肠癌患者住院虚弱风险评分与不良住院预后的关系

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-05-06 DOI: 10.1038/s41416-026-03385-2

Hao-Tsai Cheng, Chen-June Seak, Ching-Yi Cheng, Shu-Wei Huang, Chang-Mu Sung, Tsung-Hsing Chen

{"title":"The association between hospital frailty risk score and adverse inpatient outcomes in older adults with colorectal cancer.","authors":"Hao-Tsai Cheng, Chen-June Seak, Ching-Yi Cheng, Shu-Wei Huang, Chang-Mu Sung, Tsung-Hsing Chen","doi":"10.1038/s41416-026-03385-2","DOIUrl":"https://doi.org/10.1038/s41416-026-03385-2","url":null,"abstract":"Background: Impact of frailty on prognosis in patients with metastatic and non-metastatic colorectal cancer (CRC) was studied.Methods: Patients aged ≥60 years with CRC were identified in Nationwide Inpatient Sample database and analyzed retrospectively. Frailty was defined when Hospital Frailty Risk Score ≥5. Patients were grouped and matched by metastatic status. Logistic and linear regression were used to assess association between frailty and in-hospital outcomes.Results: After matching, 99,017 metastatic and 418,435 non-metastatic CRC were included. Frailty was significantly associated with increased in-hospital mortality (metastatic: OR = 1.10, 95% CI 1.05-1.17; non-metastatic: aOR = 1.05, 95% CI 1.00-1.10), prolonged length of stay (metastatic: OR = 1.30, 95% CI 1.26-1.34; non-metastatic: aOR = 1.37, 95% CI 1.34-1.39), and discharge to long-term care (metastatic: OR = 1.67, 95% CI 1.62-1.73; non-metastatic: aOR = 2.10, 95% CI 2.07-2.14). Frailty was also associated with higher total hospital costs, with additional $3,750 (95% CI $2940-$4560) in metastatic CRC and $1920 (95% CI $1480-$2360) in non-metastatic CRC.Conclusions: Frailty is an independent predictor of adverse outcomes among older patients with CRC, regardless of metastatic status.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833751","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

Changes in Cyclin E1 expression and CCNE1 amplification in high-grade ovarian carcinomas post-PARP inhibitor exposure. parp抑制剂暴露后高级别卵巢癌细胞周期蛋白E1表达和CCNE1扩增的变化

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-05-05 DOI: 10.1038/s41416-026-03440-y

Alexis Trecourt, Alexander Valent, Elisa Yaniz-Galende, Etienne Rouleau, Juan Francisco Grau Bejar, Félix Blanc-Durand, Elodie Edmond, Audrey Le Formal, Catherine Genestie, Alexandra Leary

{"title":"Changes in Cyclin E1 expression and CCNE1 amplification in high-grade ovarian carcinomas post-PARP inhibitor exposure.","authors":"Alexis Trecourt, Alexander Valent, Elisa Yaniz-Galende, Etienne Rouleau, Juan Francisco Grau Bejar, Félix Blanc-Durand, Elodie Edmond, Audrey Le Formal, Catherine Genestie, Alexandra Leary","doi":"10.1038/s41416-026-03440-y","DOIUrl":"https://doi.org/10.1038/s41416-026-03440-y","url":null,"abstract":"Background: Therapeutic options are limited for patients with high-grade ovarian carcinoma (HGOC) progressing after poly(adenosine diphosphate-ribose) polymerase-inhibitor (PARPi). WEE1/CDK2-inhibitors efficacy is under investigation in HGOC harbouring CCNE1 amplification/Cyclin E1 overexpression. However, Cyclin E1 expression evolution after PARPi has not been studied. We aimed to describe Cyclin E1 expression/CCNE1 copy number in post-PARPi HGOC samples and compare to paired samples from diagnosis and/or post-neoadjuvant chemotherapy (post-NACT).Methods: Thirty-eight patients with available post-PARPi samples were included; paired samples from diagnosis (n = 26) and/or post-NACT (n = 24) were collected. Cyclin E1 expression was quantified using immunohistochemistry (IHC). CCNE1 copy number was evaluated using fluorescent in situ hybridisation (FISH).Results: Seventy-two percent (26/36) of HGOC were homologous recombination deficient. Intratumoral Cyclin E1 expression was homogenous in samples from synchronous but anatomically distinct tumour sites. However, Cyclin E1 expression increased significantly between diagnosis and progression post-PARPi (median H-score = 113 versus 163, respectively; p = 0.034). The proportion of Cyclin E1-high (H-score ≥ 150) tumours was 31% (8/26) at diagnosis, 42% (10/24) post-NACT, and increased significantly to 61% (23/38) post-PARPi (versus diagnosis; p = 0.024). In contrast, only 10% (2/20) of Cyclin E1-high HGOC exhibited CCNE1 amplification ( ≥ 8 CCNE1 copies).Conclusions: Cyclin E1 expression in HGOC increases at post-PARPi progression, independently of CCNE1 amplification.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833651","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

Blocking mitochondrial leucine transamination enhances T-cell activation and improves T-cell immunity against OVA-producing EL4 lymphoma. 阻断线粒体亮氨酸转氨化可增强t细胞活化，提高t细胞对产生ova的EL4淋巴瘤的免疫力。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-05-05 DOI: 10.1038/s41416-026-03455-5

Christie M Adam, Tanner J Wetzel, Sheila C Erfan, Leighton M Wheeler, Emily E Baer, Lindsey P Croll, Alexander M Martin, Taha Z Khan, Max L Swain, Michael P Boyer, Elitsa A Ananieva

{"title":"Blocking mitochondrial leucine transamination enhances T-cell activation and improves T-cell immunity against OVA-producing EL4 lymphoma.","authors":"Christie M Adam, Tanner J Wetzel, Sheila C Erfan, Leighton M Wheeler, Emily E Baer, Lindsey P Croll, Alexander M Martin, Taha Z Khan, Max L Swain, Michael P Boyer, Elitsa A Ananieva","doi":"10.1038/s41416-026-03455-5","DOIUrl":"https://doi.org/10.1038/s41416-026-03455-5","url":null,"abstract":"Background: T-cell metabolism is targeted by cancer cells in an attempt to escape immune surveillance. The mitochondrial branched-chain aminotransferase, BCATm, is overexpressed in cancer, yet its role in T-cell immunity is suggested but understudied.Methods: C57BL/6 mice with T-cell specific-single BCATm deficiency were used to determine the impact of BCATm on T-cell function in vitro and in vivo using the murine EL4-OVA lymphoma. The studies were complemented by a transcriptomic correlation analysis of BCATm in human T cells and by using siRNA to knock-down BCATm in Jurkat T cells.Results: The loss of BCATm from CD4+ T cells increased mitochondrial respiration but reduced the coupling between oxygen consumption and ATP synthesis, redirecting the cells to glycolysis. This compensation sustained T-cell functionality as seen by increased release of IFN-γ from CD4+ T cells or granzyme B and perforin from CD8+ T cells. Human studies further suggested that BCATm negatively affected T-cell mitochondria. While EL4-OVA tumours from T-BCATmKO mice were enriched in memory precursor CD4+ and CD8+ T cells, reduced EL4-OVA lymphoma growth was achieved in mice with T cells carrying a combined deletion of BCATm and BCATc.Conclusions: BCATm is an immunosuppressive enzyme that may weaken T-cell performance in the lymphoma microenvironment.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833741","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

Urinary proteome and metabolome uncover tumor microenvironment and cellular metabolism changes of renal clear cell carcinoma. 尿蛋白质组学和代谢组学揭示了肾透明细胞癌的肿瘤微环境和细胞代谢变化。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-05-05 DOI: 10.1038/s41416-026-03434-w

Xiaoyan Liu, Mingxin Zhang, Yi Zhao, Yuting Dai, Chongxu Han, Jing Chen, Haidan Sun, Zhengguang Guo, Feng Qi, Yuxue Zhang, Yushi Zhang, Haitao Niu, Wei Sun

{"title":"Urinary proteome and metabolome uncover tumor microenvironment and cellular metabolism changes of renal clear cell carcinoma.","authors":"Xiaoyan Liu, Mingxin Zhang, Yi Zhao, Yuting Dai, Chongxu Han, Jing Chen, Haidan Sun, Zhengguang Guo, Feng Qi, Yuxue Zhang, Yushi Zhang, Haitao Niu, Wei Sun","doi":"10.1038/s41416-026-03434-w","DOIUrl":"https://doi.org/10.1038/s41416-026-03434-w","url":null,"abstract":"Background: Clear cell renal carcinoma (ccRCC) is the most frequent form of kidney tumors with high recurrence and progression rates. Early diagnosis of ccRCC could significantly improve survival rate. Liquid biopsies could capture molecular information which would not only shed more light on the signatures of the onset of ccRCC, but also discover potential biomarker for early diagnosis.Method: We applied LC-MS to profile the urine proteome and metabolome of 314 ccRCC, 341 healthy control and 49 kidney benign disease enrolled from three cohorts. Further cell origin annotation and protein-protein correlation analysis were performed to explain the possible TME mechanistic.Results: We revealed significant changes of extracellular matrix (ECM) organization, complement and coagulation cascades, amino acid metabolism and fatty acid metabolism in ccRCC. Cell origin annotation of cancer proteins revealed the potential role of myofibroblast cell during ECM organization. Finally, we discovered six potential urinary biomarkers, FGB,CILP, ITIH1, GUCA2B, anserine, oxindole and established models for ccRCC diagnosis with the AUC value of 0.84, 0.80 and 0.86 for protein model, metabolites model and multi-omics model in an external cohort. The protein model also showed discriminatory ability for ccRCC and benign with the AUC value of 0.75.Conclusion: Present study provided urinary molecular changes, which could reflect TME disorder and cellular metabolism reprogramming.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833891","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

Delving into tRNA-derived small RNAs in multiple myeloma: elevated 3'U-tRF^SerTGA leads to poor disease prognosis. 多发性骨髓瘤中trna衍生小rna的研究：3'U-tRFSerTGA升高导致疾病预后不良

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-05-04 DOI: 10.1038/s41416-026-03447-5

Konstantinos Soureas, Panagiotis Malandrakis, Maria-Alexandra Papadimitriou, Ioannis Ntanasis-Stathopoulos, Katerina-Marina Pilala, Christine-Ivy Liacos, Maria Gavriatopoulou, Efstathios Kastritis, Meletios-Athanasios Dimopoulos, Andreas Scorilas, Evangelos Terpos, Margaritis Avgeris

{"title":"Delving into tRNA-derived small RNAs in multiple myeloma: elevated 3'U-tRFSerTGA leads to poor disease prognosis.","authors":"Konstantinos Soureas, Panagiotis Malandrakis, Maria-Alexandra Papadimitriou, Ioannis Ntanasis-Stathopoulos, Katerina-Marina Pilala, Christine-Ivy Liacos, Maria Gavriatopoulou, Efstathios Kastritis, Meletios-Athanasios Dimopoulos, Andreas Scorilas, Evangelos Terpos, Margaritis Avgeris","doi":"10.1038/s41416-026-03447-5","DOIUrl":"https://doi.org/10.1038/s41416-026-03447-5","url":null,"abstract":"Background: Multiple myeloma (MM) is an incurable malignancy, marked by treatment resistance and frequent relapses, posing ongoing challenges to patients' long-term management. Herein, we have examined tRNA-derived small RNA fragments (3'U-tRFs), generated from precursor tRNAs, to identify MM-related 3'U-tRFs in ameliorating MM precision prognostics.Methods: 3'U-tRF profiles were generated by small RNA-seq data. Target prediction and gene ontology analysis were assessed by tRFtarget and DAVID databases, respectively. CD138 + 3'U-tRFSerTGA levels were quantified in our MM screening cohort (n = 136 patients) by RT-qPCR. Kaplan-Meier and Cox proportional regression analyses were performed, using disease progression and patients' mortality as clinical endpoints. Internal validation was conducted by bootstrap Cox regression while clinical benefit on patients' prognosis was assessed by decision curve analysis (DCA).Results: Small RNA-seq data analysis highlighted the significantly increased 3'U-tRFSerTGA levels in MM cell lines compared to normal cells (FC: 14.03). Our screening cohort confirmed the significantly higher risk for short-term progression and worse survival of the patients presenting elevated 3'U-tRFSerTGA. 3'U-tRFSerTGA-fitted multivariate models demonstrated superior risk-stratification of the patients for treatment response and prognosis.Conclusions: Our study indicate the elevated 3'U-tRFSerTGA as a strong independent predictor of poor first-line chemotherapy outcomes and MM progression, providing refined stratification of patient risk.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833686","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

Ethnic and social inequities in oral cancer in Latin America-a call for regional vigilance. 拉丁美洲口腔癌的种族和社会不平等——呼吁区域警惕。

IF 6.8 1区医学

British Journal of Cancer Pub Date : 2026-05-04 DOI: 10.1038/s41416-026-03462-6

Carlos M Ardila

引用次数: 0