British Journal of Cancer最新文献

{"title":"Correction: Targeting ADAM-17 with an inhibitory monoclonal antibody has antitumour effects in triple-negative breast cancer cells.","authors":"F Caiazza, P M McGowan, M Mullooly, A Murray, N Synnott, N O'Donovan, L Flanagan, C J Tape, G Murphy, J Crown, M J Duffy","doi":"10.1038/s41416-025-02973-y","DOIUrl":"https://doi.org/10.1038/s41416-025-02973-y","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD44⁺ cells enhance pro-tumor stroma in the spatial landscape of colorectal cancer leading edge.","authors":"Feiyu Tang, Yongwei Zhu, Jia Shen, Bowen Yuan, Xiang He, Yuxi Tian, Liang Weng, Lunquan Sun","doi":"10.1038/s41416-025-02968-9","DOIUrl":"10.1038/s41416-025-02968-9","url":null,"abstract":"<p><strong>Background: </strong>The heterogeneity of tumors significantly impacts on colorectal cancer (CRC) progression. However, the influence of this heterogeneity on the spatial architecture of CRC remains largely unknown.</p><p><strong>Methods: </strong>Spatial transcriptomic (ST) analysis of AOM/DSS-induced colorectal cancer (CRC), integrated with single-cell RNA sequencing, generated a comprehensive spatial atlas of CRC. Pseudotime trajectory, stemness evaluation, and cell-cell communication analyses explored how CD44⁺ tumor cells at the leading edge remodel the tumor microenvironment (TME). In vitro experiments and immunofluorescence staining of clinical samples validated pleiotrophin (PTN) signaling in promoting cancer-associated fibroblasts (CAFs) phenotypic transition and CRC progression.</p><p><strong>Results: </strong>Our findings revealed a distinctive layered ring-like structure within CRC tissues, where CD44⁺ tumor cells exhibiting high stemness were positioned at the tumor's leading edge. Inflammatory CAFs (iCAFs)-like, myofibroblastic CAFs (myCAFs)-like cells and pro-tumorigenic neutrophils primarily located at the tumor edge, in proximity to CD44⁺ tumor cells. CD44⁺ tumor cells then triggered the phenotypic transition of CAFs into iCAF-like and myCAF-like cells through PTN signaling.</p><p><strong>Conclusions: </strong>Our results provide distinctive insights into how tumor heterogeneity reshapes the TME at the leading edge of tumor, thereby promoting CRC progression.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The epigenetic basis of hepatocellular carcinoma - mechanisms and potential directions for biomarkers and therapeutics.","authors":"Hong-Yi Lin, Ah-Jung Jeon, Kaina Chen, Chang Jie Mick Lee, Lingyan Wu, Shay-Lee Chong, Chukwuemeka George Anene-Nzelu, Roger Sik-Yin Foo, Pierce Kah-Hoe Chow","doi":"10.1038/s41416-025-02969-8","DOIUrl":"https://doi.org/10.1038/s41416-025-02969-8","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the sixth leading cancer worldwide and has complex pathogenesis due to its heterogeneity, along with poor prognoses. Diagnosis is often late as current screening methods have limited sensitivity for early HCC. Moreover, current treatment regimens for intermediate-to-advanced HCC have high resistance rates, no robust predictive biomarkers, and limited survival benefits. A deeper understanding of the molecular biology of HCC may enhance tumor characterization and targeting of key carcinogenic signatures. The epigenetic landscape of HCC includes complex hallmarks of 1) global DNA hypomethylation of oncogenes and hypermethylation of tumor suppressors; 2) histone modifications, altering chromatin accessibility to upregulate oncogene expression, and/or suppress tumor suppressor gene expression; 3) genome-wide rearrangement of chromatin loops facilitating distal enhancer-promoter oncogenic interactions; and 4) RNA regulation via translational repression by microRNAs (miRNAs) and RNA modifications. Additionally, it is useful to consider etiology-specific epigenetic aberrancies, especially in viral hepatitis and metabolic dysfunction-associated steatotic liver disease (MASLD), which are the main risk factors of HCC. This article comprehensively explores the epigenetic signatures in HCC, highlighting their potential as biomarkers and therapeutic targets. Additionally, we examine how etiology-specific epigenetic patterns and the integration of epigenetic therapies with immunotherapy could advance personalized HCC treatment strategies.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statin use and risk of breast cancer among women with benign breast disease: a Danish nationwide cohort study.","authors":"Charlotte Skriver, Deirdre Cronin-Fenton, Signe Borgquist, Jakob Hansen Viuff, Sara Alkner, Lisa Rydén, Anne-Vibeke Lænkholm, Jonas Manjer, Ylva Bengtsson, Kirsten Frederiksen, Søren Friis, Lene Mellemkjær","doi":"10.1038/s41416-025-02974-x","DOIUrl":"https://doi.org/10.1038/s41416-025-02974-x","url":null,"abstract":"<p><strong>Background: </strong>Statins have been suggested to protect against breast cancer risk, but the observational evidence is inconclusive. We examined the association between statin use and breast cancer incidence among women at higher risk of breast cancer due to a history of benign breast disease (BBD).</p><p><strong>Methods: </strong>Using Danish registries, we identified cancer-free women aged ≥50 years during 1996-2018 with a history of BBD and no prior statin prescriptions. Using Cox regression, we estimated multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for invasive breast cancer through 2020 with time-varying statin use defined according to continuity, duration, and intensity (estimated average daily dose), derived from prescription data.</p><p><strong>Results: </strong>Among 111,550 women, 7629 were diagnosed with breast cancer during median follow-up of 12.2 years. Overall statin use was not associated with breast cancer incidence (adjusted HR = 0.99; 95% CI, 0.93-1.06), with similar associations observed according to continuity and duration of use. However, long-term (≥10 years), high-intensity statin use was associated with a reduced HR of 0.75 (95% CI, 0.60-0.96).</p><p><strong>Conclusions: </strong>Our findings did not indicate an association for overall statin use with breast cancer incidence among women with BBD. The inverse association with long-term, high-dose statin use requires further evaluation.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxic tumor cell line lysate-pulsed dendritic cell vaccine exhibits better therapeutic effects on hepatocellular carcinoma.","authors":"Long-Bin Jeng, Fu-Ying Shih, Yu-Wen Liao, Woei-Cherng Shyu, Chiao-Fang Teng","doi":"10.1038/s41416-025-02975-w","DOIUrl":"10.1038/s41416-025-02975-w","url":null,"abstract":"<p><strong>Background: </strong>Dendritic cell (DC) vaccine is a promising immunotherapy for hepatocellular carcinoma (HCC) via triggering antigen-specific anti-tumor immunity. Hypoxia contributes to higher level and broader spectrum of antigen expression in tumor cells.</p><p><strong>Methods: </strong>This study aims to compare immunological activity and therapeutic efficacy between hypoxic and normoxic HCC cell line lysate-pulsed DC vaccines.</p><p><strong>Results: </strong>The results showed that hypoxic HCC cell line lysate-pulsed DC vaccines exhibited a stronger activity in producing interleukin-12 and promoting T cell proliferation and cytotoxicity in vitro. In HCC mice, hypoxic HCC cell line lysate-pulsed DC vaccines displayed a better efficacy in improving survival time and tumor volume and inducing intratumoral cytotoxic T cell infiltration and activation as well as tumor cell apoptosis. Adenylate kinase 4-derived antigens were important for hypoxic HCC cell line lysate-pulsed DC vaccine-elicited T cell killing.</p><p><strong>Conclusions: </strong>In conclusion, this study demonstrated hypoxic HCC cell line lysate-pulsed DC vaccine as a potential therapeutic strategy for HCC.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of epigenetics in paediatric cancer pathogenesis & drug resistance.","authors":"Jia Yu Leung, Hsin Yao Chiu, Reshma Taneja","doi":"10.1038/s41416-025-02961-2","DOIUrl":"https://doi.org/10.1038/s41416-025-02961-2","url":null,"abstract":"<p><p>Paediatric oncogenesis is tightly intertwined with errors in developmental processes involving cell specification and differentiation, which are governed by intricate temporal epigenetic signals. As paediatric cancers are characterised by a low number of somatic mutations, dysregulated chromatin landscapes are believed to be key drivers of oncogenesis. Epigenetic dysregulation is induced by mutations and aberrant expression of histones and epigenetic regulatory genes, to altered DNA methylation patterns and dysregulated noncoding RNA expression. In this review, we discuss epigenetic alterations in paediatric cancer oncogenesis and recurrence, and their potential as diagnostic biomarkers. We also discuss various epigenetic drugs that have entered clinical trials for aggressive paediatric cancers. Targeting paediatric-specific epigenetic vulnerabilities may improve recurrence-free survival in high-risk cancers.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stroma AReactive Invasion Front Areas (SARIFA), tumour immune microenvironment, and survival in colorectal cancer.","authors":"Vilja V Tapiainen, Päivi Sirniö, Hanna Elomaa, Henna Karjalainen, Ville K Äijälä, Meeri Kastinen, Akseli Kehusmaa, Vesa-Matti Pohjanen, Outi Lindgren, Onni Sirkiä, Maarit Ahtiainen, Olli Helminen, Erkki-Ville Wirta, Jukka Rintala, Juha Saarnio, Tero Rautio, Toni T Seppälä, Jan Böhm, Jukka-Pekka Mecklin, Anne Tuomisto, Markus J Mäkinen, Juha P Väyrynen","doi":"10.1038/s41416-025-02972-z","DOIUrl":"https://doi.org/10.1038/s41416-025-02972-z","url":null,"abstract":"<p><strong>Background: </strong>SARIFA (Stroma AReactive Invasion Front Areas), defined as the direct contact between a tumour cell cluster and adipose cells at the invasion margin, has been proposed as a prognostic marker in gastrointestinal cancers. We hypothesized that SARIFA is associated with an immunosuppressive tumour microenvironment.</p><p><strong>Methods: </strong>SARIFA status was evaluated in two large colorectal cancer cohorts (N = 1876). Survival analyses were performed using multivariable Cox regression. Immune cell densities were analysed utilizing multiplex and conventional immunohistochemistry combined with digital image analysis.</p><p><strong>Results: </strong>SARIFA-positivity was independently associated with a shorter cancer-specific survival in both cohorts [Cohort 1: hazard ratio (HR) for SARIFA-positive (vs. negative) 1.75 (95% CI 1.35-2.25), P < 0.0001; Cohort 2: HR for SARIFA-positive (vs. negative) 2.09 (95% CI 1.43-3.05), P = 0.0001]. SARIFA-positivity was associated with lower densities of CD3⁺ T cells, CD66b⁺ granulocytes, M1-like macrophages, and CD14⁺HLA-DR⁺ mature monocytic cells, but higher densities of M2-like macrophages and CD14⁺HLA-DR^- immature monocytic cells. Mean Cohen's kappa for SARIFA evaluation between eight investigators was 0.80.</p><p><strong>Conclusions: </strong>SARIFA status is a highly reproducible, independent prognostic factor in colorectal cancer. SARIFA-positivity is associated with lower densities of antitumourigenic immune cells and the polarisation of macrophages towards a protumourigenic M2-like phenotype.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective internal radiation with Y-90 resin microspheres (SIRT) for liver metastases of gastro-intestinal stromal tumors (GIST) resistant to tyrosine kinase inhibitor (TKI) therapy.","authors":"Peter Hohenberger, Nils Rathmann, Karen Büsing, Franka Menge, Jens Jakob, Daniel Pink, Eva Wardelmann, Stefan O Schoenberg, Steffen J Diehl","doi":"10.1038/s41416-025-02952-3","DOIUrl":"https://doi.org/10.1038/s41416-025-02952-3","url":null,"abstract":"<p><strong>Background: </strong>Hepatic metastases of GIST might be the dominant site of progression and resistant to available tyrosine kinase inhibitors (TKIs). Selective internal radiation therapy (SIRT) offers treatment by intratumoral radiation up to 200 Gy. We analyzed the hepatic progression-free survival (H-PFS) in a consecutive patient cohort.</p><p><strong>Methods: </strong>Twenty-six patients (median age 57.6 years) with biopsy proven liver metastases of GIST were treated by SIRT. All had RECIST documented tumor progression, and 24/26 patients had up to four lines of pretreatment. Mutational status was 'quadruple wildtype' (q-wt, n = 5), KIT exon 11/9/13 in n = 15/4/1 cases and PDGFRα (n = 1). Median follow-up of this retrospective analysis of a prospectively kept database is 33.6 months.</p><p><strong>Results: </strong>Median H-PFS was 16 months (range, 4-54+ months, 95% CI 6.5-25.4 months) and OS after SIRT was 28 months (95% CI 17.2-28.7 months). Best H-PFS was observed in patients with 'q-wt' at 25 months (range, 6+-54 months, 95% CI 16.2-33.8 months). The worst outcome was for KIT exon 11 mutations plus secondary mutations with 7 months (range, 4-33 months, 95% CI, 4.2-9.8 months).</p><p><strong>Conclusions: </strong>90Y-SIRT is a potent treatment for patients with liver metastases of GIST resistant to TKI therapy. In patients with 'q-wt' GIST, SIRT is an option for first-line use.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EphB4-ephrin-B2 are targets in castration resistant prostate cancer.","authors":"Grace Xiuqing Li, Binyun Ma, Shaobing Zhang, Ren Liu, Imran N Siddiqi, Akash Sali, Anthony El-Khoueiry, Mitchell Gross, Bodour Salhia, Sarmad Sadeghi, Parkash S Gill","doi":"10.1038/s41416-025-02942-5","DOIUrl":"10.1038/s41416-025-02942-5","url":null,"abstract":"<p><strong>Background: </strong>PI3K pathway activation is a common and early event in prostate cancer, from loss of function mutations in PTEN, or activating mutations in PIK3Ca or AKT leading to constitutive activation, induction of growth factor-receptors kinase EphB4 and its ligand ephrin-B2. We hypothesized that induction of EphB4 is an early event required for tumor initiation. Secondly, we hypothesized that EphB4 remains relevant when prostate cancer becomes androgen independent.</p><p><strong>Methods: </strong>Genetic mouse model of conditional PTEN deletion in prostate epithelium induces tumor in all mice. We tested this model against EPHB4 wild type and deleted in prostate epithelium. This allowed us to test its role in tumor initiation. We also tested an orthogonal approach by using decoy soluble EphB4 to block bidirectional signaling resulting from EphB4-ephrin-B2 interaction. Role of EphB4-ephrin-B2 in androgen deprived mice was tested for role in refractory cancer model.</p><p><strong>Results: </strong>PTEN deletion induces EphB4 and ephrin-B2 in prostate cancer which was substantially reduced when EPHB4 is deleted in the same prostate epithelial cells. sEphB4-alb fusion protein with improved pharmacokinetics similarly inhibited tumor formation, thus establishing the role in tumor initiation. sEphB4-alb retained the efficacy in castration resistant androgen independent prostate cancer. We have thus observed that induction of EphB4 is required for the initiation of prostate cancer in PTEN null mouse and that signaling downstream from EphB4 is required in androgen deprivation and thus castration resistant prostate cancer. Pharmacological inhibition of EphB4 pathway reproduced the results. Targeting EphB4 should be tested in prostate cancer especially those resistant to androgen deprivation therapy.</p><p><strong>Conclusions: </strong>EphB4 and ephrin-B2 receptor ligand pair is induced in PTEN null prostate cancer, which significantly contributes to the tumor initiation. Secondly, EphB4-ephrin-B2 pathway continue to promote tumor progression even in androgen deprivation and thus hormone refractory tumor. EphB4-ephrin-B2 may be candidates for precision medicine with biomarker-based patient selection with and without concurrent standard of care.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential cellular origins of the extracellular matrix of tumor and normal tissues according to colorectal cancer subtypes.","authors":"Hyun Jin Lee, Sang Woo Park, Jun Hyeong Lee, Shin Young Chang, Sang Mi Oh, Siwon Mun, Junho Kang, Jong-Eun Park, Jung Kyoon Choi, Tae Il Kim, Jin Young Kim, Pilnam Kim","doi":"10.1038/s41416-025-02964-z","DOIUrl":"https://doi.org/10.1038/s41416-025-02964-z","url":null,"abstract":"<p><strong>Background: </strong>Understanding the proteomic-level heterogeneity of the tumor microenvironment (TME) in colorectal cancer (CRC) is crucial due to its well-known heterogeneity. While heterogenous CRC has been extensively characterized at the molecular subtype level, research into the functional heterogeneity of fibroblasts, particularly their relationship with extracellular matrix (ECM) alterations, remains limited. Addressing this gap is essential for a comprehensive understanding of CRC progression and the development of targeted therapies.</p><p><strong>Methods: </strong>24 tissue samples from 21 CRC patients, along with adjacent normal tissues (NAT), were collected and decellularized using a detergent-based method to enrich the ECM component. Proteomic analysis of ECM-enriched samples was performed using tandem mass tag (TMT) spectrometry, followed by statistical analysis including differential expression protein (DEP) analysis. Single-cell RNA sequencing (scRNA-Seq) data from public datasets were integrated and analyzed to delineate cell states within the TME. Bulk tissue RNA-Seq and bioinformatics analysis, including consensus molecular subtype (CMS) classification and single-cell level deconvolution of TCGA bulk RNA-seq data, were conducted to further explore gene expression patterns and TME composition.</p><p><strong>Results: </strong>Differential cellular origin of the NAT and tumorous ECM proteins were identified, revealing 110 ECM proteins enriched in NAT and 28 ECM proteins in tumor tissues. Desmoplastic and WNT5A⁺ inflammatory fibroblasts were indicated as the sources of tumor-enriched ECM proteins, while ADAMDEC1⁺ expressing fibroblasts and PI16⁺ expressing fibroblast were identified as the sources of NAT-enriched ECM proteins. Deconvolution of bulk RNA-seq of CRC tissues discriminated CMS-specific fibroblast state, reflecting the biological traits of each CMS subtype. Specially, seven ECM genes specific to mesenchymal subtype (CMS4), including PI16⁺ fibroblast-related 4 genes (SFRP2, PRELP, OGN, SRPX) and desmoplastic fibroblast-related 3 genes (THBS2, CTHRC1, BGN), showed a significant association with poorer survival in patient with CRC.</p><p><strong>Conclusion: </strong>We conducted an extracellular matrix (ECM)-focused profiling of the TME by integrating quantitative proteomics with single-cell RNA sequencing (scRNA-seq) data from CRC patients. We identified the ECM proteins of NAT and tumor tissue, and established a cell-matrisome database. We defined mesenchymal subtype-specific molecules associated with specific fibroblast subtypes showing a significant association with poorer survival in patients with CRC. Our ECM-focused profiling of tumor stroma provides new insights as indicators for biological processes and clinical endpoints.</p>","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540198","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}