Journal of the National Cancer Center最新文献

{"title":"Night shift work and breast cancer risk – 2023 update of epidemiologic evidence","authors":"Johnni Hansen,&nbsp;Julie Elbæk Pedersen","doi":"10.1016/j.jncc.2024.07.004","DOIUrl":"10.1016/j.jncc.2024.07.004","url":null,"abstract":"<div><h3>Introduction</h3><div>Night shift work is a complex and frequent occupational exposure, and breast cancer stands as the most prevalent cancer in women. The International Agency for Research on Cancer (IARC) has twice classified night shift work as a probable breast carcinogen, with the latest classification in June 2019. Since that time, new epidemiologic data has emerged.</div></div><div><h3>Methods</h3><div>We searched PubMed for original articles based on cohort and case-control studies of “breast cancer and night shift work” published after the IARC evaluation in June 2019.</div></div><div><h3>Results</h3><div>In total six cohorts and four case-control studies were included in our review. Overall, we observed some support for associations between persistent (long duration or high frequency) night shift work and an increase in breast cancer risk, though most studies were relatively small and statistically under-powered. Moreover, the recent studies do not contribute further evidence regarding the interaction with menopausal status, diurnal preference, hormonal subtypes of breast cancer or gene-environment aspects, which were issues that were left from the IARC evaluation.</div></div><div><h3>Conclusions</h3><div>The available new results somewhat consolidate the epidemiological evidence from IARC's 2019 evaluation, and do not provide further evidence regarding interaction of interest, e.g. menopausal status, etc. Therefore, long term follow-up of prospective cohorts or nested case-control studies, including precise exposure assessment and examinations of relevant interactions such as menopausal status, diurnal preference, hormonal subtypes of breast cancer and gene-environment aspects, are warranted. Meanwhile, protective measures for the night workers should be considered.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 94-103"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Efficacy and safety of paclitaxel liposome versus paclitaxel in combination with carboplatin in the first-line chemotherapy for ovarian cancer: a multicenter, open-label, non-inferiority, randomized controlled trial’ [Journal of the National Cancer Center 4 (2024) 135–141]","authors":"Rong Li ,&nbsp;Hongping Zhang ,&nbsp;Qingshui Li ,&nbsp;Guangwen Yuan ,&nbsp;Yanjie Zhou ,&nbsp;Rutie Yin ,&nbsp;He Wang ,&nbsp;Chunyan Wang ,&nbsp;Yi Huang ,&nbsp;Wei Wang ,&nbsp;Xiaojian Yan ,&nbsp;Lingying Wu ,&nbsp;Qi Zhou","doi":"10.1016/j.jncc.2024.11.002","DOIUrl":"10.1016/j.jncc.2024.11.002","url":null,"abstract":"","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Page 93"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell spatial immune profiling for precision immunotherapy in Lynch syndrome","authors":"Ramadhani Chambuso ,&nbsp;Stephene S Meena","doi":"10.1016/j.jncc.2024.12.002","DOIUrl":"10.1016/j.jncc.2024.12.002","url":null,"abstract":"<div><div>Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) predisposition syndrome, characterized by a high mutational burden and microsatellite instability-high (MSI-H) tumors. Immunology of LS-associated CRC (LS-CRC) is unique, with significant implications for treatment. Despite well-established knowledge of LS immunology, immunotherapy dose and treatment response can vary significantly based on local tumor immunity and specific germline pathogenic variant of LS genes. This variability necessitates tailored surveillance strategies and new personalised immunotherapy approaches for LS patients. LS-CRC often benefits from immunotherapy due to the distinct tumor microenvironment (TME) and the variety of tumor infiltrating lymphocytes (TILs). This perspective discusses a novel approach of analysing spatial TILs at a single-cell level using tumor whole slide images (WSIs) that accounts for the distinct TME of LS-CRC. By emphasizing the necessity of personalized medicine in hereditary cancer syndromes, the future research and clinical practices that enhance patient outcomes through precision oncology is inspired.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 3-7"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link","authors":"Alanoud Abdulla ,&nbsp;Hana Q. Sadida ,&nbsp;Jayakumar Jerobin ,&nbsp;Imadeldin Elfaki ,&nbsp;Rashid Mir ,&nbsp;Sameer Mirza ,&nbsp;Mayank Singh ,&nbsp;Muzafar A. Macha ,&nbsp;Shahab Uddin ,&nbsp;Khalid Fakhro ,&nbsp;Ajaz A. Bhat ,&nbsp;Ammira S. Al-Shabeeb Akil","doi":"10.1016/j.jncc.2024.11.001","DOIUrl":"10.1016/j.jncc.2024.11.001","url":null,"abstract":"<div><div>Obesity, a global health concern, is associated with severe health issues like type 2 diabetes, heart disease, and respiratory complications. It also increases the risk of various cancers, including melanoma, endometrial, prostate, pancreatic, esophageal adenocarcinoma, colorectal carcinoma, renal adenocarcinoma, and pre-and post-menopausal breast cancer. Obesity-induced cellular changes, such as impaired CD8⁺ T cell function, dyslipidemia, hypercholesterolemia, insulin resistance, mild hyperglycemia, and fluctuating levels of leptin, resistin, adiponectin, and IL-6, contribute to cancer development by promoting inflammation and creating a tumor-promoting microenvironment rich in adipocytes. Adipocytes release leptin, a pro-inflammatory substance that stimulates cancer cell proliferation, inflammation, and invasion, altering the tumor cell metabolic pathway. Adiponectin, an insulin-sensitizing adipokine, is typically downregulated in obese individuals. It has antiproliferative, proapoptotic, and antiangiogenic properties, making it a potential cancer treatment. This narrative review offers a comprehensive examination of the molecular interconnections between obesity and cancer, drawing on an extensive, though non-systematic, survey of the recent literature. This approach allows us to integrate and synthesize findings from various studies, offering a cohesive perspective on emerging themes and potential therapeutic targets. The review explores the metabolic disturbances, cellular alterations, inflammatory responses, and shifts in the tumor microenvironment that contribute to the obesity-cancer link. Finally, it discusses potential therapeutic strategies aimed at disrupting these connections, offering valuable insights into future research directions and the development of targeted interventions.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 8-27"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese expert consensus on flow cytometric detection of hematological malignant cells in tissue samples","authors":"Zailin Yang ,&nbsp;Xia Mao ,&nbsp;Mingxia Zhu ,&nbsp;Shuang Chen ,&nbsp;Zifen Gao ,&nbsp;Tingting Jiang ,&nbsp;Yu Peng ,&nbsp;Fanggang Ren ,&nbsp;Huijun Wang ,&nbsp;Lili Wang ,&nbsp;Suigui Wan ,&nbsp;Xiangqin Weng ,&nbsp;Chunyan Wang ,&nbsp;Yujie Wu ,&nbsp;Yazhe Wang ,&nbsp;Yonggang Xu ,&nbsp;Jie Zhu ,&nbsp;Mingqing Zhu ,&nbsp;Yaping Zhai ,&nbsp;Hongmei Jing ,&nbsp;Yanrong Liu","doi":"10.1016/j.jncc.2024.11.003","DOIUrl":"10.1016/j.jncc.2024.11.003","url":null,"abstract":"<div><div>Flow cytometry (FCM), characterized by its simplicity, rapid processing, multiparameter analysis, and high sensitivity, is widely used in the diagnosis, treatment, and prognosis of hematological malignancies. FCM testing of tissue samples not only aids in diagnosing and classifying hematological cancers, but also enables the detection of solid tumors. Its ability to detect numerous marker parameters from small samples is particularly useful when dealing with limited cell quantities, such as in fine-needle biopsy samples. This attribute not only addresses the challenge posed by small sample sizes, but also boosts the sensitivity of tumor cell detection. The significance of FCM in clinical and pathological applications continues to grow. To standardize the use of FCM in detecting hematological malignant cells in tissue samples and to improve quality control during the detection process, experts from the Cell Analysis Professional Committee of the Chinese Society of Biotechnology jointly drafted and agreed upon this consensus. This consensus was formulated based on current literature and clinical practices of all experts across clinical, laboratory, and pathological fields in China. It outlines a comprehensive workflow of FCM-based assay for the detection of hematological malignancies in tissue samples, including report content, interpretation, quality control, and key considerations. Additionally, it provides recommendations on antibody panel designs and analytical approaches to enhancing FCM tests, particularly in cases with limited sample sizes.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 28-37"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatments of transarterial chemoembolization (TACE), stereotactic body radiotherapy (SBRT) and immunotherapy reshape the systemic tumor immune environment (STIE) in patients with unresectable hepatocellular carcinoma","authors":"Cai-Ning Zhao ,&nbsp;Chi-Leung Chiang ,&nbsp;Wan-Hang Keith Chiu ,&nbsp;Sik-Kwan Kenneth Chan ,&nbsp;Chun-Bong James Li ,&nbsp;Wei-Wei Chen ,&nbsp;Dan-Yang Zheng ,&nbsp;Wen-Qi Chen ,&nbsp;Ren Ji ,&nbsp;Chung-Mau Lo ,&nbsp;Salma K. Jabbour ,&nbsp;Chi-Yan Albert Chan ,&nbsp;Feng-Ming (Spring) Kong","doi":"10.1016/j.jncc.2024.06.007","DOIUrl":"10.1016/j.jncc.2024.06.007","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The role of systemic tumor immune environment (STIE) is unclear in hepatocellular carcinoma (HCC). This study aimed to exam the cells in the STIE, their changes after transarterial chemoembolisation (TACE), stereotactic body radiotherapy (SBRT), and immunotherapy (IO) and explore their significance in the treatment response of patients with unresectable HCC.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This is a prospective biomarker study of patients with unresectable HCC. The treatment was sequential TACE, SBRT (27.5–40 Gy/5 fractions), and IO. The treatment response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) by magnetic resonance imaging (MRI) after 6 months of treatment. Longitudinal data of STIE cells was extracted from laboratory results of complete blood cell counts, including leukocytes, lymphocytes, neutrophils, monocytes, eosinophils, basophils, and platelets. Peripheral blood samples were collected at baseline and after TACE, SBRT, and IO for T-lymphocyte subtyping by flow cytometry. Generalized estimation equation was employed for longitudinal analyses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 35 patients with unresectable HCC were enrolled: 23 patients in the exploratory cohort and 12 in the validation cohort. STIE circulating cells, especially lymphocytes, were heterogenous at baseline and changed differentially after TACE, SBRT, and IO in both cohorts. SBRT caused the greatest reduction of 0.7 × 10&lt;sup&gt;9&lt;/sup&gt;/L (95 % CI: 0.3 × 10&lt;sup&gt;9&lt;/sup&gt;/L–1.0 × 10&lt;sup&gt;9&lt;/sup&gt;/L, &lt;em&gt;P&lt;/em&gt; &lt; 0.001) in lymphocytes; less reduction was associated with significantly better treatment response. The analysis of T-lymphocyte lineage revealed that the baseline levels of CD4&lt;sup&gt;+&lt;/sup&gt; T cells (&lt;em&gt;P&lt;/em&gt; = 0.010), type 1 T helper (Th1) cells (&lt;em&gt;P&lt;/em&gt; = 0.007), and Th1/Th17 ratios (&lt;em&gt;P&lt;/em&gt; = 0.001) were significantly higher in responders, while regulatory T (Treg) cells (&lt;em&gt;P&lt;/em&gt; = 0.002), Th17 cells (&lt;em&gt;P&lt;/em&gt; = 0.047), and Th2/Th1 ratios (&lt;em&gt;P&lt;/em&gt; = 0.028) were significantly higher in non-responders. After treatment with TACE, SBRT and IO, T-lymphocyte lineage also changed differentially. More reductions were observed in CD25&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells and CD127&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells after SBRT in non-responders, while increases in natural killer T (NKT) cells after SBRT (10.4% vs. 3.4 %, &lt;em&gt;P&lt;/em&gt; = 0.001) and increases in the lymphocyte counts were noted during IO in responders.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;STIE cells are significant for treatment response, can be reshaped differentially after TACE, SBRT, and IO. The most significant changes of T-lymphocyte lineage are SBRT associated modulations in CD25&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells, CD127&lt;sup&gt;+&lt;/sup&gt;CD8&lt;sup&gt;+&lt;/sup&gt; T cells, and NKT cells, which also have significant effects on the ultimate treatment response after TACE-SBRT-IO (ClinicalTrails.gov identifier: GCOG0001/NC","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 38-49"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated molecular characterization reveals the pathogenesis and therapeutic strategies of pulmonary blastoma","authors":"He Tian ,&nbsp;Zhenlin Yang ,&nbsp;Junhui Yang ,&nbsp;Ying Chen ,&nbsp;Lin Li ,&nbsp;Tao Fan ,&nbsp;Tiejun Liu ,&nbsp;Guangyu Bai ,&nbsp;Yibo Gao ,&nbsp;Jie He","doi":"10.1016/j.jncc.2024.12.001","DOIUrl":"10.1016/j.jncc.2024.12.001","url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary blastoma (PB) is a rare subtype of lung cancer. Currently, the underlying pathogenesis mechanisms of PB have not been fully illustrated, and the therapeutic approach for this entity is limited.</div></div><div><h3>Methods</h3><div>Whole-exome sequencing (WES), RNA sequencing, and DNA methylation profiling are applied to seven PB patients. Multi-omics data of pulmonary sarcomatoid carcinoma (PSC) and pituitary blastoma (PitB) from previous studies are invoked to illuminate the associations among PB and these malignacies.</div></div><div><h3>Results</h3><div>We portray the genomic alteration spectrum of PB and find that <em>DICER1</em> is with the highest alteration rate (86 %). We uncover that <em>DICER1</em> alterations, Wnt signaling pathway dysregulation and IGF2 imprinting dysregulation are the potential pathogenesis mechanisms of PB. Moreover, we reveal that the integrated molecular features of PB are distinct from PSC, and the molecular characteristics of PB are more similar to PitB than to PSC. Pancancer analysis show that the tumor mutation burden (TMB) and leukocyte fraction (LF) of PB are low, while some cases are positive for PD-L1 or have CD8-positive focal areas, implying the potential applicability of immunotherapy in selected PB patients.</div></div><div><h3>Conclusion</h3><div>This study depicts the integrated molecular characteristics of PB and offers novel insights into the pathogenesis and therapeutic strategies of PB.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 82-92"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ADRIATIC study: revolutionizing the standard treatment paradigm for concurrent chemoradiotherapy in limited-stage small cell lung cancer","authors":"Banzhou Pan,&nbsp;Bo Shen","doi":"10.1016/j.jncc.2024.12.003","DOIUrl":"10.1016/j.jncc.2024.12.003","url":null,"abstract":"","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 1-2"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time and space co-ordinates of Hodgkin's lymphoma in Sardinia, Italy","authors":"Giorgio Broccia ,&nbsp;Jonathan Carter ,&nbsp;Cansu Ozsin-Ozler ,&nbsp;Sara De Matteis ,&nbsp;Pierluigi Cocco","doi":"10.1016/j.jncc.2024.05.006","DOIUrl":"10.1016/j.jncc.2024.05.006","url":null,"abstract":"<div><h3>Background</h3><div>The epidemiological investigation of Hodgkin's lymphoma (HL) among the genetically peculiar population of the Italian island of Sardinia might provide interesting etiological clues.</div></div><div><h3>Methods</h3><div>We used the database of 1974–2003 incident cases of hematological malignancies in Sardinia and Bayesian methods to explore the time trend and geographic spread of HL incidence by sex, and age whether ≤44 or ≥45 years. We also tested its association with several socio-economic and environmental risk factors.</div></div><div><h3>Results</h3><div>The age- and sex-standardized (world population) incidence rate of HL was 2.6 per 100,000 (95% CI, 2.5–2.8). Over the study period, HL incidence increased linearly in both sexes and among those aged ≤44 years but not above that age<em>.</em> Cases clustered among young women in a central-western area covering four bordering administrative units (13 cases <em>vs.</em> 5.7 expected, <em>P</em> = 0.002). The posterior probability of excess HL cases aged ≤44 years was elevated only in a commune in the suburban area of the region's capital. Cases aged ≥45 years were uniformly spread over the region. Among the risk factors we explored, urban residence was associated with an elevated and goat farming with a decreased risk of HL occurrence. We did not observe a link with socio-economic deprivation, environmental exposures, or multiple sclerosis. The geographic spread of COVID-19 was also unrelated to past HL incidence.</div></div><div><h3>Conclusions</h3><div>Our results prompt further in-depth investigation into the previously undetected cluster and the nature of the observed associations.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 50-56"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of ornithine decarboxylase 1 mediates the immune-deserted microenvironment and poor prognosis in diffuse large B-cell lymphoma","authors":"Xiaojie Liang ,&nbsp;Jia Guo ,&nbsp;Xiaofang Wang ,&nbsp;Baiwei Luo ,&nbsp;Ruiying Fu ,&nbsp;Haiying Chen ,&nbsp;Yunong Yang ,&nbsp;Zhihao Jin ,&nbsp;Chaoran Lin ,&nbsp;Aimin Zang ,&nbsp;Youchao Jia ,&nbsp;Lin Feng ,&nbsp;Liang Wang","doi":"10.1016/j.jncc.2024.10.001","DOIUrl":"10.1016/j.jncc.2024.10.001","url":null,"abstract":"<div><h3>Background</h3><div>Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lymphoma (DLBCL). However, subgroups with dismal prognosis and stem cell-like characteristics have been overlooked.</div></div><div><h3>Methods</h3><div>Using large scale data (<em>n</em> = 2133), we conducted machine learning algorithms to identify a high risk DLBCL subgroup with stem cell-like features, and then investigated the potential mechanisms in shaping this subgroup using transcriptome, genome and single-cell RNA-seq data, and <em>in vitro</em> experiments.</div></div><div><h3>Results</h3><div>We identified a high-risk subgroup (25.6 % of DLBCL) with stem cell-like characteristics and dismal prognosis. This high-risk group (HRG) was featured by upregulation of key enzyme (ODC1) in polyamine metabolism and cold tumor microenvironment (TME), and had a poor prognosis with lower 3-year overall survival (OS) (54.3 % vs. 83.6 %, <em>P</em> &lt; 0.0001) and progression-free survival (PFS) (42.8 % vs. 74.7 %, <em>P</em> &lt; 0.0001) rates compared to the low-risk group. HRG also exhibited malignant proliferative phenotypes similar to Burkitt lymphoma. Patients with <em>MYC</em> rearrangement, double-hit, double-expressors, or complete remission might have either favorable or poor prognosis, which could be further distinguished by our risk stratification model. Genomic analysis revealed widespread copy number losses in the chemokine and interferon coding regions 8p23.1 and 9p21.3 in HRG. We identified ODC1 as a therapeutic vulnerability for HRG-DLBCL. Single-cell analysis and <em>in vitro</em> experiments demonstrated that ODC1 overexpression enhanced DLBCL cell proliferation and drove macrophage polarization towards the M2 phenotype. Conversely, ODC1 inhibition reduced DLBCL cell proliferation, induced cell cycle arrest and apoptosis, and promoted macrophage polarization towards the M1 phenotype. Finally, we developed a comprehensive database of DLBCL for clinical application.</div></div><div><h3>Conclusions</h3><div>Our study effectively advances the precise risk stratification of DLBCL and reveals that ODC1 and immune-deserted microenvironment jointly shape a group of DLBCL patients with stem cell-like features. Targeting ODC1 regulates immunotherapies in DLBCL, offering new insights for DLBCL treatment.</div></div>","PeriodicalId":73987,"journal":{"name":"Journal of the National Cancer Center","volume":"5 1","pages":"Pages 57-74"},"PeriodicalIF":7.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}