Cancer Research and Treatment最新文献

{"title":"Genomic Profiling Identified a Mutational Signature Related to Female in Non-Smoking Lung Adenocarcinoma.","authors":"Jinman Zhuang, Yongsheng Yang, Xuezhen Chen, Guanying Zheng, Xiaopei Shen, Fei He, Baosong Xie","doi":"10.4143/crt.2025.489","DOIUrl":"https://doi.org/10.4143/crt.2025.489","url":null,"abstract":"<p><strong>Purpose: </strong>Our aim was to illustrate mutational characteristic in non-smoking lung adenocarcinoma (LUAD) and to explore its relationship with clinical factors.</p><p><strong>Materials and methods: </strong>We included 86 non-smokers with LUAD and downloaded the clinical information, whole exon sequencing (WES), and RNA sequencing (RNA-seq) data from cBioPortal and TCGA website. NMF algorithm, \"SomaticSignatures\", and \"DeconstructSigs\" were used to re-construct and infer new mutational signature. The similarity between COSMIC and re-constructed mutational signature was measured by cosine similarity. The enrichment status of signaling pathways was derived by GSEA. \"pRRophetic\" package was used to predict the sensitivity of adjuvant drug for cancer treatments.</p><p><strong>Results: </strong>The most frequent driver genes in non-smoking LUAD were EGFR (59% in cBioPortal cohort, 68% in Fujian non-smoking LUAD cohort). We identified three new mutation signatures of LUAD in non-smokers and identified S2 as the most enriched signature in these non-smokers with LUAD. In cBioPortal and Fujian non-smoking LUAD cohort, the proportion of S2 was higher in females (p<0.05) and patients with TMB (p<0.01). Similar results were observed in non-smoking TCGA-LUAD cohort (Pfemale=0.0013, PTMB<0.001). OXIDATIVE_PHOSPHORYLATION signaling pathway were most enriched in S2-enriched group (NES= 1.63). S2-enriched group had higher mutation rate of EGFR (p=0.003) and more drug sensitivity to metformin (p=0.035).</p><p><strong>Conclusion: </strong>We identified a new mutational signature (S2) which is most enriched in LUAD in non-smokers and related to female and low-TMB. S2 mutational signature may help revealed female-related mutagenesis mechanisms and develop strategies for therapeutic of never-smoker lung adenocarcinoma.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine-Primed MSCs Enhance Antitumor Immunity-Associated Gene Expression Without Promoting AML Cell Growth.","authors":"Na Hee Lee, Byungchan Kim, Keon Hee Yoo","doi":"10.4143/crt.2025.583","DOIUrl":"https://doi.org/10.4143/crt.2025.583","url":null,"abstract":"<p><strong>Purpose: </strong>Mesenchymal stromal cells (MSCs), while regarded as promising immunomodulatory tools, have raised concerns in recent studies for their potential to promote tumor growth or facilitate immune evasion. These risks are particularly relevant in hematologic malignancies, where MSCs have been used to mitigate graft-versus-host disease or support hematopoietic engraftment. This study aimed to evaluate the effects of cytokine-primed MSCs on acute myeloid leukemia (AML) cells, with a focus on both safety and immunomodulatory efficacy.</p><p><strong>Materials and methods: </strong>Wharton's jelly-derived MSCs were primed with interferon-gamma (IFN-γ), interleukin-6, lipopolysaccharide, and tumor necrosis factor-alpha, followed by co-cultured with AML cell lines. AML cell viability was measured by CCK-8 assay. RNA sequencing and qPCR were performed to assess gene expression profiles under each priming condition.</p><p><strong>Results: </strong>Cytokine priming MSC did not result in significant changes in AML cell viability (p > 0.05), supporting the safety of this approach. Meanwhile, IFN-γ priming significantly upregulated genes involved in immune modulation and apoptosis, including IDO1, TNFSF10, ICAM1, and chemokines CXCL9, CXCL10, and CXCL11.</p><p><strong>Conclusion: </strong>Cytokine priming, particularly with IFN-γ, enhanced the immunomodulatory gene expression of MSCs without promoting AML cell proliferation. Although direct cytotoxic effects were not observed in co-culture experiments, the absence of increased leukemic cell growth under any priming condition supports the biological safety of this approach. These findings provide a strong foundation for further in vivo studies to assess the therapeutic applicability of primed MSCs in hematologic malignancies while ensuring oncologic safety.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk-Stratified Management of ADC drug-Related Neutropenia: Integrating Clinical Trial Meta-Summary and Existing Guideline Principles.","authors":"Zheling Chen, Keju Zhao, Jiahong Jiang, Liu Yang","doi":"10.4143/crt.2025.533","DOIUrl":"https://doi.org/10.4143/crt.2025.533","url":null,"abstract":"<p><strong>Purpose: </strong>Anti-tumor drugs have developed rapidly in recent years. Antibody-drug conjugates (ADCs), as a novel class of targeted biologics, demonstrate significant survival benefits but inevitably cause treatment-related toxicities, with hematologic toxicity-particularly severe neutropenia (grade ≥3)-representing the most prevalent and clinically consequential adverse effect. Currently, no standardized ADC-specific neutropenia management guidelines exist, resulting in fragmented prevention strategies where clinical practice relies on extrapolation from chemotherapy protocols and reactive approaches (e.g., post-onset growth factor support). This study aims to address this gap by proposing a structured preventive framework for ADC-induced neutropenia.</p><p><strong>Materials and methods: </strong>We conducted a systematic meta-summary of neutropenia data from clinical trials involving ADCs. This evidence was integrated with established principles from chemotherapy-induced neutropenia guidelines and expert consensus. The analysis focused on drug-specific risk profiles, patient-related factors, and evidence-based interventional strategies.</p><p><strong>Results: </strong>We developed a risk-adapted preventive strategy centered on a \"planning for a rainy day\" approach. The framework incorporates: (1) risk stratification based on the specific ADC drug and patient factors; (2) primary prophylaxis with long-acting granulocyte colony-stimulating factor (G-CSF) for high-risk patients; (3) secondary prevention strategies for subsequent treatment cycles; and (4) dynamic monitoring of absolute neutrophil counts (ANC) around days 5-7 post-infusion.</p><p><strong>Conclusion: </strong>Shifting from a reactive to a proactive, personalized prevention paradigm can potentially reduce the incidence of severe neutropenia, subsequent treatment interruptions, and infection-related mortality. This framework provides actionable guidance for standardizing ADC toxicity management and underscores the importance of prioritizing hematologic safety in future ADC development.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Neoadjuvant Systemic Therapy May Serve as an Indicator for Omitting Post-BCS Radiation Therapy in Women with Early-Stage Breast Cancer.","authors":"Chaofan Li, Yusheng Wang, Mengjie Liu, Shiyu Sun, Yiwei Jia, Jingkun Qu, Shuqun Zhang, Chong Du","doi":"10.4143/crt.2025.584","DOIUrl":"https://doi.org/10.4143/crt.2025.584","url":null,"abstract":"<p><strong>Purpose: </strong>To avoid unnecessary toxicities and optimize the allocation of healthcare resources, it is crucial to adequately select patients with extremely low recurrence risk to downgrade or eliminate radiation therapy.</p><p><strong>Materials and methods: </strong>From the SEER database, clinical data of 7,291 female patients with early-stage breast cancer who underwent neoadjuvant systemic therapy (NST) and breast-conserving surgery (BCS) were collected for this study. The patients were stratified by their response to NST, and the long-term survival, and risk of recurrence were assessed using Cox regression analysis and Fine-gray competing risk models for those with and without post-BCS RT, respectively.</p><p><strong>Results: </strong>Our results showed that female with early-stage breast cancer who achieved complete response (CR) to NST, omitting post-BCS RT achieved the same OS and DFS as those who received the post-BCS RT, and the omission did not increase the risk of recurrence or BCSD. For patients who did not achieve CR to NST, five clinical indicators (including age, N stage, grade, response to NST, and molecular subtype) were employed to construct a nomogram for clinical prediction of the risk of recurrence. The validated results affirmed our model's ability to accurately discriminate high- and low-risk patients and its promising clinical application value.</p><p><strong>Conclusion: </strong>Post-BCS RT can be omitted for women with early-stage breast cancer who achieved CR to NST. For those who failed to achieve CR to NST, a nomogram was constructed for clinicians to decide whether to omit post-BCS RT or not based on the individualized assessment.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of T Cell Subsets Using Multiplex Immunohistochemistry and Clinical Outcomes of Immune Checkpoint Inhibitors in Advanced Gastric Cancer Patients.","authors":"Tae-Yong Kim, Jeesun Yoon, Dae-Won Lee, Yoonjin Kwak, Hye Seung Lee, Do-Youn Oh","doi":"10.4143/crt.2025.458","DOIUrl":"https://doi.org/10.4143/crt.2025.458","url":null,"abstract":"<p><strong>Purpose: </strong>As immunotherapy has become essential in the treatment of gastric cancer (GC), there has been growing interest in T-cells, which play a key role in immunotherapy. In this study, we evaluated the impact of T-cell subsets on immune responsiveness to immune checkpoint inhibitors (ICIs) in GC using multiplex immunohistochemistry (mIHC).</p><p><strong>Materials and methods: </strong>Eighty-four GC patients treated with ICIs were enrolled, and we repeated the staining-scanning-stripping procedure nine times to assess different kinds of T-cells or cell-surface immune checkpoints in a single tissue section.</p><p><strong>Results: </strong>The proportions of patients with microsatellite instability-high (MSI-H), Epstein-Barr virus (EBV), and non-MSI/non-EBV were 8.3%, 3.6% and 88.1%. A high cytotoxic T-cell (Tcyto) density was related to longer overall survival (OS). GC with a high ratio of Tcyto/total T-cells (Ttotal) and a low ratio of regulatory T-cells (Treg)/Ttotal showed better OS. A high density of PD-1- or TIM-3- expressing Tcyto were also associated with longer OS than a low density of those. Among memory T-cells (Tmem) subsets, GC with a high ratio of memory Tcyto/Tmem and a low ratio of memory Treg/Tmem showed prolonged OS. Better tumor responses were observed in GC with a high ratio of Tcyto/Ttotal and memory Tcyto/Tmem.</p><p><strong>Conclusion: </strong>T-cell subsets within the tumor microenvironment were associated with the clinical efficacy of ICIs in GC. PD-1- or TIM-3 expressing T-cells were also associated with response to ICIs, while memory T-cells subsets were associated with survival. mIHC is a feasible method for evaluating T-cell subsets in archival gastric tumor tissue.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Anticancer Effects of Lenvatinib and Celastrol via ROS-Mediated ER Stress and JNK Signaling in Colon Cancer Cells.","authors":"Ying Yan, Chenyu Qiu, Wenying Fu, Chongchong Shu, Chenxin Xu, Yinghua Chen, Yiqun Xia, Jundixia Chen, Yunzhi Chen, Ri Cui, Peng Zou, Daoyong Ni","doi":"10.4143/crt.2025.508","DOIUrl":"https://doi.org/10.4143/crt.2025.508","url":null,"abstract":"<p><strong>Purpose: </strong>Colon cancer, a predominant contributor to global cancer mortality, is characterized by uncontrolled cell growth in the colon or rectum. Therapeutic progress notwithstanding, including targeted therapies and chemotherapy, the survival rate remains unsatisfactory, especially for patients with advanced colon cancer, underscoring the need for novel strategies to enhance treatment efficacy.</p><p><strong>Materials and methods: </strong>In this study, we employed Western blot analysis to quantify target protein expression levels and immunofluorescence for protein detection and localization. To evaluate drug interactions, we calculated the Combination Index (CI). Intracellular ROS levels were measured using the DCFH-DA probe. Additionally, we generated target gene-knockdown cell lines via recombinant lentivirus transfection. For in vivo validation, we established a xenograft tumor model in nude mice to assess the therapeutic efficacy of the drug combination.</p><p><strong>Results: </strong>In the study, we systematically evaluated the combinatorial potential of clinically approved lenvatinib and bioactive celastrol against colorectal cancer pathogenesis. Our results demonstrated that the combination treatment significantly inhibited cancer cell proliferation by enhancing reactive oxygen species (ROS) generation. This oxidative stress activated the ATF4-CHOP and JNK signaling pathways, ultimately inducing cell apoptosis as the main cause of death phenomenon.</p><p><strong>Conclusion: </strong>Our research demonstrates that celastrol potentiates lenvatinib's anti-tumor effects in colon cancer by inducing ROS-dependent ER stress and triggering phosphorylation-dependent JNK pathway activation. These findings revealing a promising combinatorial strategy to enhance therapeutic efficacy in colorectal carcinoma.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive Assessment of Ki-67 Expression in Breast Cancer Using Ultrasound Radiomics: A Multi-Institutional Study.","authors":"Sijie Mo, Zhibin Huang, Jing Zheng, Huaiyu Wu, Shuzhen Tang, Mengyun Wang, Jinfeng Xu, Hongtian Tian, Xiaoli Huang, Fajin Dong","doi":"10.4143/crt.2025.581","DOIUrl":"https://doi.org/10.4143/crt.2025.581","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop and rigorously evaluate machine learning models using ultrasound (US) breast cancer (BC) images to predict Ki-67 expression. Additionally, the study sought to identify independent factors influencing Ki-67 expression, with further test conducted through external datasets.</p><p><strong>Materials and methods: </strong>This study analyzed US images of BC from 347 patients (training set: n = 230; external test set: n=117) from Shenzhen People's Hospital and Guangxi Academy of Medical Sciences. Radiomic features were extracted using manual region-of-interest (ROI) delineation and the Pyradiomics package. Feature selection was performed using LASSO and decision tree analysis, resulting in 16 features. Machine learning models-logistic regression (LR), support vector machine (SVM), and multilayer perceptron (MLP)-were developed, and their performance was assessed using the area under the receiver operating characteristic curve (ROC), accuracy, sensitivity, specificity, and decision curve analysis. Statistical analysis included univariate and multivariate logistic regression.</p><p><strong>Results: </strong>Three machine learning models (LR, SVM, MLP) were developed to predict Ki-67 expression from US images. The LR model demonstrated the best diagnostic performance, with an AUC of 0.800 in external test set. Key predictors of Ki-67 expression included ill-defined mass maximum Maximum diameter and HER2 expression, along with other significant clinical variables.</p><p><strong>Conclusion: </strong>This dual-center study demonstrates the potential of radiomics models based on US BC images to predict Ki-67 expression accurately. As a non-invasive diagnostic tool, this approach offers valuable support for clinical decision-making and personalized treatment planning in BC patients.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Healthy Behaviors and All-cause Mortality among Korean Gastric Cancer Survivors.","authors":"Donghyun Won, Jeeyoo Lee, Sooyoung Cho, Ji Yoon Baek, Hyuk-Joon Lee, Aesun Shin","doi":"10.4143/crt.2025.177","DOIUrl":"https://doi.org/10.4143/crt.2025.177","url":null,"abstract":"<p><strong>Purpose: </strong>The incidence, prevalence and survival rates of gastric cancer are high, and the prognostic effects of healthy behaviors among survivors have not been well investigated. Therefore, We aimed to assess the effects of postdiagnosis healthy behaviors and behavior changes after gastric cancer diagnosis on all-cause mortality.</p><p><strong>Materials and methods: </strong>As a population-based retrospective cohort study, we used a cancer public library sample DB of gastric cancer patients between 2012 and 2019. Information from regular health check-up examinations were used to investigate their anthropometric measures, physical activities, alcohol consumption, and smoking status before and after cancer diagnosis. Hazard ratios (HRs) for all-cause deaths with 95% confidence intervals (CIs) were estimated via the Cox proportional hazards model.</p><p><strong>Results: </strong>We analyzed 9,717 gastric cancer patients and 5,929 of those as a subgroup to assess the effects of behavior changes. Reduced mortality was shown among cancer patients who met the recommended criteria after the cancer diagnosis for physical activity (adjusted HR = 0.67 [95% CI=0.49-0.93], mean frequencies of moderate to vigorous physical activity per week: ≥5 days vs. 0 days) and smoking cessation (0.77 [0.61-0.97], smoking status: never-smokers vs. current smokers). Participants who reported enhancement in behaviors had significantly lower mortality than the others who reported no or limited changes in physical activity (0.73 [0.55-0.96]) and smoking status (0.56 [0.38-0.83]).</p><p><strong>Conclusion: </strong>The current study highlights the advantages of physical activity and smoking cessation in reducing mortality, and these benefits are even greater when patients improve their behavior after cancer diagnosis.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H3K18la Facilitates TRA2A-Mediated Alternative Splicing of STIL, Suppressing Ferroptosis and Cisplatin Treatment Sensitivity in Ovarian Cancer.","authors":"Mingyang Gao, Shiming Wang, Zhiyuan Huang, Tianliang Wang, Yuexin Yu","doi":"10.4143/crt.2025.752","DOIUrl":"https://doi.org/10.4143/crt.2025.752","url":null,"abstract":"<p><strong>Purpose: </strong>Ovarian cancer (OC) is a common and highly lethal malignant tumor in women. Due to its hidden early symptoms, most patients are diagnosed at an advanced stage, and the tumor often develops resistance to chemotherapy, making treatment challenging. Elucidating the mechanisms of OC development and identifying new therapeutic targets, are crucial for improving treatment outcomes.</p><p><strong>Materials and methods: </strong>We used bioinformatics analysis combined with qRT-PCR, WB, and IHC to study TRA2A expression and histone lactylation in OC samples. CCK8, clone formation, EdU, and Transwell experiments were used to assess OC cells proliferation. RT-PCR analyzed TRA2A-mediated alternative splicing. And the nude mouse xenograft model was constructed to validate TRA2A's molecular function in vivo.</p><p><strong>Results: </strong>This study reveals a novel mechanism by which OC cells evade ferroptosis through the TRA2A-STIL signaling axis. Specifically, H3K18la is significantly enriched at the promoter region of the TRA2A gene, activating its transcription and upregulating expression. The upregulated TRA2A protein, functioning as a key splicing factor, specifically regulates alternative splicing (AS) of the STIL mRNA. This promotes expression of the STIL-L isoform, which inhibits ferroptosis in OC cells by modulating iron metabolism. Furthermore, targeted knockdown of TRA2A combined with cisplatin treatment significantly enhanced the therapeutic efficacy against OC. Consequently, targeting TRA2A-mediated AS represents a promising novel therapeutic target for OC.</p><p><strong>Conclusion: </strong>This study uncovers for the first time a novel mechanism by which OC cells evade ferroptosis via an H3K18la-modified TRA2A-STIL signaling axis, thereby establishing a promising new therapeutic target for OC treatment.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Role of SOCS1 Mutations in Diffuse Large B-Cell Lymphoma.","authors":"Xin-Yi Zhang, Tong-Yao Xing, Wei Hua, Yue Li, Yi-Lin Kong, Bi-Hui Pan, Xin-Yu Zhang, Jia-Zhu Wu, Hao-Rui Shen, Hua Yin, Li Wang, Jian-Yong Li, Rui Gao, Jin-Hua Liang, Wei Xu","doi":"10.4143/crt.2025.420","DOIUrl":"https://doi.org/10.4143/crt.2025.420","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the prognostic impact of SOCS1 mutations in diffuse large B-cell lymphoma (DLBCL) and explores the underlying biological mechanisms, focusing on immune regulation and cellular metabolism.</p><p><strong>Materials and methods: </strong>We included 2,590 DLBCL patients from 7 publicly databases (integrated cohort) and 202 additional DLBCL cases from our institution (JSPH cohort). Next-generation sequencing (NGS) was used to detect SOCS1 mutations in DLBCL patients. We analyzed the association between these mutations and overall survival (OS) and progression-free survival (PFS). Additionally, we examined how SOCS1 mutations might influence immune responses, cellular metabolism, and signaling pathways, particularly in the ST2 subtypes of DLBCL.</p><p><strong>Results: </strong>In the integrated cohort, 15.1% of patients carried SOCS1 mutations, with 12.3% of these mutations located in the SOCS-BOX domain. SOCS1 mutations were found to be more frequent in the GCB and ST2 subtypes of DLBCL. In the integrated cohort, patients with SOCS1 mutations had significantly better OS (p=0.015) and PFS (p=0.007). Mutations located in the SOCS-BOX domain were associated with even better OS (p=0.015) and PFS (p=0.012). In the JSPH cohort, transcriptomic analyses indicated enhanced interferon signaling, immune activation, and downregulation of metabolic pathways in SOCS1-mut cases, especially within the ST2 subtype. These alterations may contribute to a more favorable tumor microenvironment and improved clinical outcomes.</p><p><strong>Conclusion: </strong>SOCS1 mutations, particularly those in the SOCS-BOX domain, are associated with improved prognosis in DLBCL. By promoting immune activation and inhibiting cellular metabolism, these mutations may not only serve as prognostic biomarkers but also provide insights into potential therapeutic avenues.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}