British Journal of Cancer最新文献

{"title":"Identification of a 5-gene signature panel for the prediction of prostate cancer progression","authors":"Michelle Shen, Fernando García-Marqués, Arvind Muruganantham, Shiqin Liu, James Robert White, Abel Bermudez, Meghan A. Rice, Kelsey Thompson, Chun-Liang Chen, Chia-Nung Hung, Zhao Zhang, Tim H. Huang, Michael A. Liss, Kenneth J. Pienta, Sharon J. Pitteri, Tanya Stoyanova","doi":"10.1038/s41416-024-02854-w","DOIUrl":"10.1038/s41416-024-02854-w","url":null,"abstract":"Despite nearly 100% 5-year survival for localised prostate cancer, the survival rate for metastatic prostate cancer significantly declines to 32%. Thus, it is crucial to identify molecular indicators that reflect the progression from localised disease to metastatic prostate cancer. To search for molecular indicators associated with prostate cancer metastasis, we performed proteomic analysis of rapid autopsy tissue samples from metastatic prostate cancer (N = 8) and localised prostate cancer (N = 2). Then, we utilised multiple independent, publicly available prostate cancer patient datasets to select candidates that also correlate with worse prostate cancer clinical prognosis. We identified 154 proteins with increased expressions in metastases relative to localised prostate cancer through proteomic analysis. From the subset of these candidates that correlate with prostate cancer recurrence (N = 28) and shorter disease-free survival (N = 37), we identified a 5-gene signature panel with improved performance in predicting worse clinical prognosis relative to individual candidates. Our study presents a new 5-gene signature panel that is associated with worse clinical prognosis and is elevated in prostate cancer metastasis on both protein and mRNA levels. Our 5-gene signature panel represents a potential modality for the prediction of prostate cancer progression towards the onset of metastasis.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 11","pages":"1748-1761"},"PeriodicalIF":6.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02854-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458461","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}

{"title":"Author Correction: Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus","authors":"Masashi Hashimoto, Shinji Kuroda, Nobuhiko Kanaya, Daisuke Kadowaki, Yusuke Yoshida, Masaki Sakamoto, Yuki Hamada, Ryoma Sugimoto, Chiaki Yagi, Tomoko Ohtani, Kento Kumon, Yoshihiko Kakiuchi, Kazuya Yasui, Satoru Kikuchi, Ryuichi Yoshida, Hiroshi Tazawa, Shunsuke Kagawa, Takahito Yagi, Yasuo Urata, Toshiyoshi Fujiwara","doi":"10.1038/s41416-024-02850-0","DOIUrl":"10.1038/s41416-024-02850-0","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 10","pages":"1716-1717"},"PeriodicalIF":6.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02850-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458459","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}

{"title":"Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma","authors":"Chandrani Chattopadhyay, Janos Roszik, Rajat Bhattacharya, Md Alauddin, Iqbal Mahmud, Sirisha Yadugiri, Mir Mustafa Ali, Fatima S. Khan, Varun Vijay Prabhu, Philip L. Lorenzi, Bo Wei, Elizabeth Burton, Rohini R. Morey, Rossana Lazcano, Michael A. Davies, Sapna P. Patel, Elizabeth A. Grimm","doi":"10.1038/s41416-024-02866-6","DOIUrl":"10.1038/s41416-024-02866-6","url":null,"abstract":"Uveal melanoma (UM) is a highly aggressive disease with very few treatment options. We previously demonstrated that mUM is characterized by high oxidative phosphorylation (OXPHOS). Here we tested the anti-tumor, signaling and metabolic effects of imipridones, which are CLPP activators, which inhibit OXPHOS indirectly and have demonstrated safety in patients. We assessed CLPP expression in UM patient samples. We tested the effects of imipridones (ONC201 and ONC212) on the growth, survival, signaling and metabolism of UM cell lines in vitro, and for therapeutic efficacy in vivo in UM liver metastasis models. CLPP expression was detected in primary and mUM patient samples. ONC201 and 212 decreased OXPHOS effectors, inhibited cell growth and migration, and induced apoptosis in human UM cell lines in vitro. ONC212 inhibited OXPHOS, increased metabolic stress and apoptotic pathways, inhibited amino acid metabolism, and induced cell death-related lipids. ONC212 also decreased tumor burden and increased survival in vivo in two UM liver metastasis models. Imipridones are a promising strategy for further testing and development in mUM.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 11","pages":"1846-1857"},"PeriodicalIF":6.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02866-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406146","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}

{"title":"Quiescent cancer cells induced by high-density cultivation reveals cholesterol-mediated survival and lung metastatic traits","authors":"Xingyang Liu, Qinjie Min, Xinxin Cheng, Weimin Zhang, Qingnan Wu, Xu Chen, Mengzhu Lv, Siqi Liu, Huihui Zhao, Di Yang, Yidi Tai, Xiao Lei, Yan Wang, Qimin Zhan","doi":"10.1038/s41416-024-02861-x","DOIUrl":"10.1038/s41416-024-02861-x","url":null,"abstract":"The metastatic cascade, a multifaceted and highly aggressive process, is the primary cause of mortality. The survival of quiescent cancer cells in circulatory system during metastasis is crucial, yet our comprehension is constrained by the absence of universally accepted quiescent cancer models. We developed a quiescent cancer cell model using high-density cultivation. Based on the scRNA-seq analysis, IP-MS, metabolomics, mouse lung metastasis models, cholesterol assay, PLA and other molecular experiments, we explored the molecular mechanism. Immunofluorescence, atomic force microscope, FluidFM, and shear stress stimulation were used to analyze the cytoskeleton and membrane properties contributing to mechanical force resistance. We established a quiescent cancer cell model induced by high-density cultivation. Single-cell RNA sequencing (scRNA-seq) analysis reveals that CDC25A plays a crucial role in the transition to quiescence, with its expression significantly elevated in the quiescent state. Depletion of CDC25A leads to an increased proliferative capacity, and reduced metastasis under high-density conditions. Mechanistically, upregulated CDC25A in quiescent cells enhances cholesterol metabolism via endosome pathways, leading to cell cycle arrest. This increase in cholesterol reinforces the cytoskeleton, alters membrane properties, and improves resistance to mechanical forces in circulatory system. CDC25A significantly increased the cholesterol metabolism through endosome pathway in quiescent cancer cells, leading to the significant changes in cytoskeleton and membrane properties so as to enhance the resistance of mechanical force in circulatory system, facilitating lung metastasis.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 10","pages":"1591-1604"},"PeriodicalIF":6.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02861-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399372","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}

{"title":"The SRC-family serves as a therapeutic target in triple negative breast cancer with acquired resistance to chemotherapy","authors":"Eivind Valen Egeland, Kotryna Seip, Eleni Skourti, Geir Frode Øy, Solveig J. Pettersen, Abhilash D. Pandya, Maria A. Dahle, Mads H. Haugen, Alexander Kristian, Sigve Nakken, Olav Engebraaten, Gunhild M. Mælandsmo, Lina Prasmickaite","doi":"10.1038/s41416-024-02875-5","DOIUrl":"10.1038/s41416-024-02875-5","url":null,"abstract":"Resistance to chemotherapy, combined with heterogeneity among resistant tumors, represents a significant challenge in the clinical management of triple negative breast cancer (TNBC). By dissecting molecular pathways associated with treatment resistance, we sought to define patient sub-groups and actionable targets for next-line treatment. Bulk RNA sequencing and reverse phase protein array profiling were performed on isogenic patient-derived xenografts (PDX) representing paclitaxel-sensitive and -resistant tumors. Pathways identified as upregulated in the resistant model were further explored as targets in PDX explants. Their clinical relevance was assessed in two distinct patient cohorts (NeoAva and MET500). Increased activity in signaling pathways involving SRC-family kinases (SFKs)- and MAPK/ERK was found in treatment resistant PDX, with targeted inhibitors being significantly more potent in resistant tumors. Up-regulation of SFKs- and MAPK/ERK-pathways was also detected in a sub-group of chemoresistant patients after neoadjuvant treatment. Furthermore, High SFK expression (of either SRC, FYN and/or YES1) was detected in metastatic lesions of TNBC patients with fast progressing disease (median disease-free interval 27 vs 105 months). Upregulation of SFK-signaling is found in a subset of chemoresistant tumors and is persistent in metastatic lesions. Based on pre-clinical results, these patients may respond favorably to treatment targeting SFKs.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 10","pages":"1656-1667"},"PeriodicalIF":6.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02875-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399373","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}

{"title":"Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer","authors":"Nadia Øgaard, Sarah Østrup Jensen, Mai-Britt Worm Ørntoft, Christina Demuth, Mads Heilskov Rasmussen, Tenna Vesterman Henriksen, Jesper Nors, Amanda Frydendahl, Iben Lyskjær, Marijana Nesic, Christina Therkildsen, Jakob Kleif, Mikail Gögenur, Lars Nannestad Jørgensen, Jesper Vilandt, Jakob Benedict Seidelin, Kåre Anderson Gotschalck, Claudia Jaensch, Berit Andersen, Uffe Schou Løve, Ole Thorlacius-Ussing, Per Vadgaard Andersen, Thomas Kolbro, Alessio Monti, Jeppe Kildsig, Peter Bondeven, Nis Hallundbæk Schlesinger, Lene Hjerrild Iversen, Morten Rasmussen, Ismail Gögenur, Jesper Bertram Bramsen, Claus Lindbjerg Andersen","doi":"10.1038/s41416-024-02867-5","DOIUrl":"10.1038/s41416-024-02867-5","url":null,"abstract":"Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.g. by including a ‘low-ctDNA-shedding’ and ‘less-aggressive’ subgroup. ctDNA assessment was performed in two independent cohorts of consecutively recruited patients with asymptomatic colorectal cancer (CRC) (Cohort#1: n = 215, Cohort#2: n = 368) and symptomatic CRC (Cohort#1: n = 117, Cohort#2: n = 722). After adjusting for tumour stage and size, the odds of ctDNA detection was significantly lower in asymptomatic patients compared to symptomatic patients (Cohort#1: OR: 0.4, 95%CI: 0.2–0.8, Cohort#2: OR: 0.7, 95%CI: 0.5–0.9). Further, the recurrence risk was lower in asymptomatic patients (Cohort#1: sHR: 0.6, 95%CI: 0.3–1.2, Cohort#2: sHR: 0.6, 95%CI: 0.4–1.0). Notably, ctDNA-negative asymptomatic patients had the lowest recurrence risk compared to the symptomatic patients (Cohort#1: sHR: 0.2, 95%CI: 0.1–0.6, Cohort#2: sHR: 0.3, 95%CI: 0.2–0.6). Our study suggests that asymptomatic patients are enriched for a ‘low-ctDNA-shedding-low-recurrence-risk’ subgroup. Such insights are needed to guide ctDNA-based early-detection initiatives and should prompt discussions about de-escalation of therapy and follow-up for ctDNA-negative asymptomatic CRC patients.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 10","pages":"1707-1715"},"PeriodicalIF":6.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41416-024-02867-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399371","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}

{"title":"A Myc-SED mechanism?","authors":"Giovambattista Pani","doi":"10.1038/s41416-024-02876-4","DOIUrl":"10.1038/s41416-024-02876-4","url":null,"abstract":"","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 9","pages":"1399-1399"},"PeriodicalIF":6.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388219","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":"Whole tumour- and subregion-based radiomics of contrast-enhanced mammography in differentiating HER2 expression status of invasive breast cancers: A double-centre pilot study","authors":"Simin Wang, Ting Wang, Sailing Guo, Shuangshuang Zhu, Ruchuan Chen, Jinlong Zheng, Tingting Jiang, Ruimin Li, Jinhui Li, Jiawei Li, Xigang Shen, Min Qian, Meng Yang, Shengnan Yu, Chao You, Yajia Gu","doi":"10.1038/s41416-024-02871-9","DOIUrl":"10.1038/s41416-024-02871-9","url":null,"abstract":"To explore the value of whole tumour- and subregion-based radiomics of contrast-enhanced mammography (CEM) in differentiating the HER2 expression status of breast cancers. 352 patients underwent preoperative CEM from two centres were consecutively enroled and divided into the training, internal validation, and external validation cohorts. The lesions were divided into HER2-positive and HER2-negative groups. Besides the radiological features, radiomics features capturing the whole tumour-based (wITH) and subregion-based intratumoral heterogeneity (sITH) were extracted from the craniocaudal view of CEM recombined images. The XGBoost classifier was applied to develop the radiological, sITH, and wITH models. A combined model was constructed by fusing the prediction results of the three models. The mean age of the patients was 51.1 ± 10.7 years. Two radiological features, four wITH features, and three sITH features were selected to establish the models. The combined model significantly improved the AUC to 0.80 ± 0.03 (95% CI: 0.73–0.86), 0.79 ± 0.06 (95% CI: 0.67–0.90), and 0.79 ± 0.05 (95% CI: 0.69–0.89) in the training, internal validation, and external validation cohorts, respectively (All P < 0.05). The combined model showed good agreement between the predicted and observed probabilities and favourable net clinical benefit in the validation cohorts. Both whole tumour- and subregion-based ITH radiomics features of CEM exhibited potential for differentiating the HER2 expression status. Combining conventional radiological features and ITH features can improve the model’s performance.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 10","pages":"1613-1622"},"PeriodicalIF":6.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388223","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 18F-FDG-PET/CT in the initial staging of very high-risk Ewing Sarcoma in a prospective multicentric Phase II Study: Is there still a place for bone marrow sampling?","authors":"Nina Jehanno, Nadège Corradini, Nathalie Gaspar, Mehdi Brahmi, Thibaud Valentin, Gabriel Revon Rivière, Cyril Lervat, Jamie Probert, Natacha Entz-Werle, Ludovic Mansuy, Dominique Plantaz, Maria Rios, Laure Saumet, Cécile Verité, Marie-Pierre Castex, Estelle Thebaud, Thibaut Cassou-Mounat, Anne-Sophie Plissonnier, Veronique Mosseri, Camille Cordero, Valerie Laurence","doi":"10.1038/s41416-024-02864-8","DOIUrl":"10.1038/s41416-024-02864-8","url":null,"abstract":"The Ewing Sarcoma Family of Tumors (ESFT) constitutes a group of rare malignancies, wherein approximately one-third of cases exhibit metastatic spread, particularly impacting prognosis when bone and/or bone marrow (BM) are involved. Primary extra-pulmonary metastatic ESFT often necessitates intensified therapeutic approaches. Accurate staging plays a pivotal role in clinical decision-making, with fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) currently serving as a non-invasive modality for assessing ESFT’s BM extent. In the French phase II COMBINAIR3 (NCT03011528) study, a comprehensive approach for patients with extra-pulmonary ESFT metastasis was evaluated. We prospectively compared the efficacy of PET/CT to BM aspiration and biopsy (BMAB) analysis in patients undergoing initial staging. Among the 42 patients analyzed (median age 14 y, 2:1 male/female ratio), 45% presented with pelvic primary tumors and 83% had bone/BM involvement at diagnosis. Our findings showed PET/CT had 100% specificity and 83.3% sensitivity in detecting initial BM involvement. Overall, PET/CT correctly classified 92.8% of patients, reaching 100% accuracy in patients identified with bone involvement, thus surpassing the standard BMAB. These results suggest that the conventional use of BMAB in the initial staging of high-risk ESFT patients can be omitted, promoting PET/CT as a non-invasive alternative, thus improving staging accuracy and treatment decisions in ESFT management.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 10","pages":"1605-1612"},"PeriodicalIF":6.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388221","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":"Serum bilirubin levels and risk of colorectal cancer in Korean adults: results from the Korean Genome and Epidemiology Study-Health Examinee (KoGES-HEXA) Cohort Study","authors":"Hwayoung Noh, Jeeyoo Lee, Nazlisadat Seyed Khoei, Laia Peruchet-Noray, Daehee Kang, Beatrice Fervers, Karl-Heinz Wagner, Aesun Shin, Heinz Freisling","doi":"10.1038/s41416-024-02847-9","DOIUrl":"10.1038/s41416-024-02847-9","url":null,"abstract":"Current evidence on associations between circulating bilirubin and colorectal cancer (CRC) risk is inconsistent. In this prospective study, we investigated associations of pre-diagnostic circulating levels of total and indirect bilirubin with CRC risk in 78,467 Korean adults aged 40–78 years at recruitment, considering potential non-linearity and sex differences. Hazard ratios (HR) and 95% confidence intervals (CI) for associations with CRC risk were estimated with Cox proportional hazard regression. During a median 7.9-year follow-up, 539 incident CRC cases were recorded. In multivariable-adjusted models, higher levels of total bilirubin were associated with a 26% (CI: 42% to 7%) lower risk of CRC among men and women combined, comparing the highest with the lowest tertile (P-linear trend = 0.003). A U-shaped association was observed in men, with the lowest risk at approximately 0.8 mg/dL (=13.7 μmol/L) of total bilirubin (P for non-linearity = 0.01). Although the association was largely null in women, there was no evidence for effect modification by sex (P-interaction = 0.73). Associations between indirect bilirubin and CRC risk were similar. Higher circulating levels of total and indirect bilirubin were inversely associated with the risk of CRC among Korean adults. The associations were strongly inverse and U-shaped among men.","PeriodicalId":9243,"journal":{"name":"British Journal of Cancer","volume":"131 10","pages":"1635-1643"},"PeriodicalIF":6.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388222","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}