Cancer Cell International最新文献

{"title":"OTUD3 inhibits breast cancer cell metastasis by regulating TGF-β pathway through deubiquitinating SMAD7.","authors":"Chenchen Geng, Ke Dong, Junhua An, Ziqian Liu, Qianqian Zhao, Yanrong Lv","doi":"10.1186/s12935-025-03822-x","DOIUrl":"10.1186/s12935-025-03822-x","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BRCA) is the most common malignant tumor in women, and distant metastasis is an important cause of death. Epithelial mesenchymal transition (EMT) is an important factor in tumor cell metastasis, in which TGF-β signaling pathway plays an important role. SMAD7 can inhibit TGF-β pathway. Previously, we found that ovarian tumor domain-containing protein 3(OTUD3) could maintain the stability of multiple molecules through deubiquitination. In this study, multiple experiments were conducted to verify whether OTUD3 can inhibit TGF-β pathway by deubiquitinating SMAD7.</p><p><strong>Methods: </strong>Firstly, bioinformatics was used to search the expression of OTUD3 in breast cancer and its correlation with SMAD7 in the TCGA database. The correlation between the protein and mRNA expression levels of OTUD3 and SMAD7 in multiple BRCA cell lines was verified. Also, the OTUD3 and SMAD7 expression in human BRCA samples and its influence on prognosis were verified by immunohistochemical experiments. Then, the CO-IP experiment was performed by transfecting OTUD3 and SMAD7 in HEK293T cells to confirm whether OTUD3 could maintain SMAD7 protein stability through deubiquitination. Furthermore, luciferase reporting assay, in vitro protein interaction, and transwell assay were used to verify whether OTUD3 could inhibit TGF-β pathway by deubiquitinating SMAD7 and affect cell invasion. Western blot and RT-qPCR were used to detect the correlation between OTUD3 and molecules regulated by the TGF-β pathway. Finally, the effect of OTUD3 on tumor cells was determined by 3D matrigel cell culture.</p><p><strong>Results: </strong>The expression of OTUD3 was low in BRCA and positively correlated with SMAD7. Cytological experiments and immunohistochemistry confirmed that OTUD3 was positively correlated with the expression of SMAD7, and the patients with a low expression of OTUD3 had a short recurrence-free survival (RFS). Cell experiments confirmed that OTUD3 could regulate the TGF-β pathway by deubiquitinating SMAD7, which affected EMT and inhibited cell invasion. OTUD3 was found to inhibit the stemness of tumor cells by 3D matrigel cell culture.</p><p><strong>Conclusions: </strong>Our findings indicated OTUD3 inhibited BRCA metastasis associated with TGF-β signaling by deubiquitination to stabilize SMAD7 protein levels.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"181"},"PeriodicalIF":5.3,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrogenesis-driven tumor progression in clear cell renal cell carcinoma: prognostic, therapeutic implications and the dual role of neuropilin-1.","authors":"Kai Wang, Xihao Shen, Jiyue Wu, Qing Bi, Zihao Gao, Zejia Sun, Wei Wang","doi":"10.1186/s12935-025-03801-2","DOIUrl":"10.1186/s12935-025-03801-2","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) is the predominant subtype of renal cancer, with a poor prognosis driven by therapy resistance and a propensity for recurrence. Tumor microenvironment (TME)-associated fibrosis accelerates disease progression by fostering immune evasion. Neuropilin-1 (NRP1), a key mediator in fibrotic signaling and cancer biology, has been implicated in these processes. However, the genetic correlation between fibrogenesis and ccRCC remains largely unexplored, necessitating a focused analysis of fibrogenesis-related genes (FRGs) to identify novel prognostic markers and therapeutic strategies.</p><p><strong>Methods: </strong>This study utilized an integrative bioinformatics framework to identify prognosis-associated fibrogenesis-related genes (pFRGs) and applied non-negative matrix factorization (NMF) to stratify ccRCC patients based on fibrotic signatures. A machine learning-derived prognostic model was developed to categorize patients into high-risk and low-risk groups, with tumor microenvironment (TME) features analyzed across these subgroups. The pro-tumorigenic role of NRP1 via the TGF-β/SMAD signaling pathway was validated in vitro and in vivo.</p><p><strong>Results: </strong>Twelve pFRGs were identified, with elevated expression correlating with reduced survival. NMF revealed two ccRCC subtypes with different fibrotic and immune profiles. The high-fibrosis subtype showed worse survival and a pro-tumorigenic TME. The risk model demonstrated robust predictive performance (AUCs: 0.738, 0.731, 0.711 for 1-, 2-, and 3-year survival). High-risk patients, marked by immune dysfunction, exhibited worse survival but greater immunotherapy sensitivity. Among the pFRGs, NRP1 was upregulated in ccRCC, and paradoxically associated with favorable prognosis in TCGA, primarily due to stromal enrichment. In vitro and in vivo experiments confirmed that NRP1 promotes ccRCC proliferation, migration, and invasion by enhancing TGF-β/SMAD-driven epithelial-mesenchymal transition (EMT).</p><p><strong>Conclusion: </strong>Fibrosis is a critical driver of ccRCC progression, linking fibrogenesis-related genes to poor prognosis, immune suppression, and tumor aggressiveness. NRP1 was identified as a central regulator of fibrosis-induced tumor progression through the TGF-β/SMAD signaling pathway. Combining NRP1 inhibition with anti-fibrotic therapies presents a potential strategy for enhancing therapeutic outcomes in ccRCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"179"},"PeriodicalIF":5.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12082889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel model for predicting immunotherapy response and prognosis in NSCLC patients.","authors":"Ting Zang, Xiaorong Luo, Yangyu Mo, Jietao Lin, Weiguo Lu, Zhiling Li, Yingchun Zhou, Shulin Chen","doi":"10.1186/s12935-025-03800-3","DOIUrl":"10.1186/s12935-025-03800-3","url":null,"abstract":"<p><strong>Background: </strong>How to screen beneficiary populations has always been a clinical challenge in the treatment of non-small-cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs). Routine blood tests, due to their advantages of being minimally invasive, convenient, and capable of reflecting tumor dynamic changes, have potential value in predicting the efficacy of ICIs treatment. However, there are few models based on routine blood tests to predict the efficacy and prognosis of immunotherapy.</p><p><strong>Methods: </strong>Patients were randomly divided into training cohort and validation cohort at a ratio of 2:1. The random forest algorithm was applied to select important variables based on routine blood tests, and a random forest (RF) model was constructed to predict the efficacy and prognosis of ICIs treatment. For efficacy prediction, we assessed receiver operating characteristic (ROC) curves, decision curve analysis (DCA) curves, clinical impact curve (CIC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) compared with the Nomogram model. For prognostic evaluation, we utilized the C-index and time-dependent C-index compared with the Nomogram model, Lung Immune Prognostic Index (LIPI) and Systemic Inflammatory Score (SIS). Patients were classified into high-risk and low-risk groups based on RF model, then the Kaplan-Meier (K-M) curve was used to analyze the differences in progression-free survival (PFS) and overall survival (OS) of patients between the two groups.</p><p><strong>Results: </strong>The RF model incorporated RDW-SD, MCV, PDW, CD3⁺CD8⁺, APTT, P-LCR, Ca, MPV, CD4⁺/CD8⁺ ratio, and AST. In the training and validation cohorts, the RF model exhibited an AUC of 1.000 and 0.864, and sensitivity/specificity of (100.0%, 100.0%) and (70.3%, 93.5%), respectively, which had superior performance compared to the Nomogram model (training cohort: AUC = 0.531, validation cohort: AUC = 0.552). The C-index of the RF model was 0.803 in the training cohort and 0.712 in the validation cohort, which was significantly higher than Nomogram model, LIPI and SIS. K-M survival curves revealed that patients in the high-risk group had significantly shorter PFS/OS than those in the low-risk group.</p><p><strong>Conclusions: </strong>In this study, we developed a novel model (RF model) to predict the response to immunotherapy and prognosis in NSCLC patients. The RF model demonstrated better predictive performance for immunotherapy responses than the Nomogram model. Moreover, when predicting the prognosis of immunotherapy, it outperformed the Nomogram model, LIPI, and SIS.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"178"},"PeriodicalIF":5.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SP1 promotes triple-negative breast cancer progression by targeting USP5.","authors":"Shi-Yi Wu, Zi-Mei Peng, Feng-Yi Deng, Jin-Yong Xiong, Pu-Ying Luo, Xiao-Jian Han, Zhen Zhang","doi":"10.1186/s12935-025-03802-1","DOIUrl":"10.1186/s12935-025-03802-1","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is characterized by the absence of targeted therapies and a dismal prognosis, necessitating a critical exploration of the molecular mechanisms driving TNBC pathogenesis and the identification of novel therapeutic targets. While dysregulated USP5 expression has been observed in various malignancies, its specific functions and mechanisms in TNBC remain poorly understood.</p><p><strong>Methods: </strong>The study utilized a combination of TCGA database analysis, immunohistochemistry staining (IHC), quantitative RT-PCR, and western blotting assay to investigate the expression of USP5 and SP1 in TNBC. Furthermore, the study examined the role of the SP1-USP5 axis and the USP5 inhibitor periplocin in TNBC progression through CCK-8 assay, colony formation assay, EDU incorporation assay, and tumor xenograft experiments. Additionally, the study explored the underlying mechanisms involved in the regulation of USP5 expression in TNBC using luciferase assay, ChIP-qPCR, quantitative RT-PCR, and western blotting assay. In order to ascertain potential inhibitors of USP5 activity, a combination of the Molecular Operating Environment (MOE) multi-functional docking platform, cellular thermal shift assay, and in vitro USP5 activity assay were utilized.</p><p><strong>Results: </strong>In the current investigation, it was observed that the expression of USP5 was elevated in TNBC and was significantly correlated with decreased overall survival rates among patients. The upregulation of USP5 was found to be mediated by the transcription factor SP1 through its binding to the USP5 promoter, consequently facilitating the progression of TNBC. Notably, the natural compound periplocin was identified as a promising inhibitor of USP5, demonstrating potential efficacy in impeding the advancement of TNBC.</p><p><strong>Conclusions: </strong>Our research findings indicate that the SP1-USP5 signaling pathway is significantly involved in the advancement of TNBC, and periplocin's ability to target USP5 presents a potential therapeutic approach for managing TNBC. These results offer valuable insights for the development of novel treatment strategies for TNBC patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"177"},"PeriodicalIF":5.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCR::ABL1 expression in chronic myeloid leukemia cells in low oxygen is regulated by glutamine via CD36-mediated fatty acid uptake.","authors":"Caterina Mancini, Giulio Menegazzi, Silvia Peppicelli, Giampaolo Versienti, Daniele Guasti, Giuseppe Pieraccini, Elisabetta Rovida, Matteo Lulli, Laura Papucci, Persio Dello Sbarba, Alessio Biagioni","doi":"10.1186/s12935-025-03805-y","DOIUrl":"https://doi.org/10.1186/s12935-025-03805-y","url":null,"abstract":"<p><strong>Background: </strong>Chronic myeloid leukemia (CML) is influenced by microenvironmental nutrients, glucose (Glc), and glutamine (Gln) which regulate cell proliferation, viability, and the expression of the driver oncoprotein (BCR::ABL1).</p><p><strong>Results: </strong>Our study revealed that Glc, while partially supporting alone cell growth in normoxia, is essential in low oxygen conditions, whereas Gln is ineffective. Under low oxygen, Gln reduced oxidative respiratory activity while enhancing glycolysis. In these conditions, fatty acid (FA) metabolism becomes crucial, as evidenced by increased lipid droplets (LD) accumulation when Glc was absent. Gln, in particular, drives CD36-mediated FA uptake, suppressing the BCR::ABL1 oncoprotein and facilitating cell survival. By co-culturing leukemia cells with adipocytes, one of the main bone marrow (BM) cell components, we observed an enhanced FA release, suggesting a link between FA, microenvironmental BM cells, and the maintenance of leukemic stem cells (LSC).</p><p><strong>Methods: </strong>K562 and KCL22 cell lines were subjected to Glc and/or Gln deprivation under hypoxic conditions (96 h at 0.1% O₂). Metabolic profiling was conducted through the Seahorse XFe96 analyzer, and the contribution of L-Glutamine-¹³C₅ to FA de novo synthesis was determined via GC/MS. Intracellular neutral LD were measured using BODIPY 493/503 in confocal microscopy and flow cytometry, with their presence and morphology further examined via transmission electron microscopy. BCR::ABL1 as well as several FA-related markers were evaluated via Western Blotting, whilst CD36 was determined through flow cytometry. LC2 assay was used for measuring leukemia stem cell potential by inhibiting FA uptake via the usage of the Sulfo-N-Succinimidyl Oleate, a CD36 inhibitor. qPCR was exploited to detect markers of FA secretion in CML-adipocytes co-culture together with Nile Red staining to assess free FA in the media.</p><p><strong>Conclusions: </strong>These findings underscore the central role of FA in the regulation of the LSC compartment of CML, highlighting the importance of Gln in facilitating CML cell survival under restrictive metabolic conditions and preparing the cell population for expansion upon the release of these restrictions.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"176"},"PeriodicalIF":5.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.","authors":"Forouzan Bahmani, Maryam Shayanmanesh, Mahdi Safari, Amirarsalan Alaei, Yasaman Pouriafar, Zahra Rasti, Farhad Zaker, Shahrbano Rostami, Fatemeh Damerchiloo, Majid Safa","doi":"10.1186/s12935-025-03793-z","DOIUrl":"https://doi.org/10.1186/s12935-025-03793-z","url":null,"abstract":"<p><p>Myelodysplastic neoplasms (MDS) represent a heterogeneous group of malignant hematopoietic stem and progenitor cell (HSPC) disorders characterized by cytopenia, ineffective hematopoiesis, as well as the potential to progress to acute myeloid leukemia (AML). The pathogenesis of MDS is influenced by intrinsic factors, such as genetic insults, and extrinsic factors, including altered bone marrow microenvironment (BMM) composition and architecture. BMM is reprogrammed in MDS, initially to prevent the development of the disease but eventually to provide a survival advantage to dysplastic cells. Recently, inflammation or age-related inflammation in the bone marrow has been identified as a key pathogenic mechanism for MDS. Inflammatory signals trigger stress hematopoiesis, causing HSPCs to emerge from quiescence and resulting in MDS development. A better understanding of the role of the BMM in the pathogenesis of MDS has opened up new avenues for improving diagnosis, prognosis, and treatment of the disease. This article provides a comprehensive review of the current knowledge regarding the significance of the BMM to MDS pathophysiology and highlights recent advances in developing innovative therapies.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"175"},"PeriodicalIF":5.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genomic landscape of esophageal squamous cell carcinoma cell lines.","authors":"Chao Zhang, Chenghao Li, Jian Zhong Su, Kuaile Zhao, Longlong Shao, Jiaying Deng","doi":"10.1186/s12935-025-03686-1","DOIUrl":"https://doi.org/10.1186/s12935-025-03686-1","url":null,"abstract":"<p><strong>Background: </strong>Research on the genomic characteristics of common esophageal squamous cell carcinoma (ESCC) cell lines, including exome mutations and mRNA expression, is limited. This study aims to elucidate the malignancy, invasion capability, classical cancer-related signaling pathways, and immune status of ESCC cell lines, providing a detailed genomic landscape and highlighting the unique features of each cell line.</p><p><strong>Methods: </strong>Whole exome and RNA sequencing were conducted on ESCC cell lines TE-1, ECA-109, KYSE-30, KYSE-150, KYSE-180, KYSE-450, and KYSE-510, with the normal epithelium cell line Het-1a as a comparison. Bioinformatics methods analyzed gene mutation types, mutation frequencies, RNA expression, and classical cancer-related signaling pathways. Specific analyses were also performed on tumor burden, genes related to differentiation, invasion, immunity, and gene enrichment in each cell line.</p><p><strong>Results: </strong>The highest tumor mutation burden (TMB) was 70.4 mutations per megabase (mut/MB) in KYSE-150, while the lowest was 48.7 mut/MB in KYSE-510. Mutations in the Hippo, Notch, PI3K, RTK-Ras, and Wnt signaling pathways were present in all cancer cell lines. Mutations were significantly enriched in signature 3, associated with defective homologous recombination deficiency (HRD). The NRF2 signaling pathway exhibited mutations in KYSE-180, KYSE-450, and TE-1 cell lines. The cell cycle gene mutation frequency was low, occurring only in KYSE-30 and TE-1 cell lines. The expression profiles of KYSE-510 and ECA-109 were similar. The KYSE-150 cell line showed up-regulated invasion genes, while the KYSE-450 cell line had significantly down-regulated poor differentiation-related genes. Immune-related genes were up-regulated in the ECA-109 cell line.</p><p><strong>Conclusion: </strong>The molecular profiles generated in this study provide detailed information on gene mutations and expression in common ESCC cell lines. The KYSE-150 cell line exhibited a prominent invasion capability, while the ECA-109 cell line showed up-regulated immune properties. This genomic landscape offers valuable insights for future research and therapeutic strategies in ESCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"174"},"PeriodicalIF":5.3,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moxibustion regulates KDM4D expression and modulates lipid metabolism to inhibit tumor proliferation in CAC mice.","authors":"Guona Li, Jindan Ma, Luyi Wu, Hanxiao Zhang, Yaying Lin, Hongxiao Xu, Muen Gu, Kunshan Li, Hongsheng Dong, Yan Huang, Huangan Wu","doi":"10.1186/s12935-025-03798-8","DOIUrl":"https://doi.org/10.1186/s12935-025-03798-8","url":null,"abstract":"<p><strong>Background: </strong>Lysine demethylase 4D (KDM4D) and aberrant lipid metabolism are implicated in the development and progression of colitis-associated cancer (CAC). Moxibustion, a therapeutic approach in traditional Chinese medicine, can inhibit intestinal inflammation and improve the intestinal mucosa.</p><p><strong>Methods: </strong>Mice were intraperitoneally injected with AOM, and three cycles of 3-2-2% DSS-free drinking water were administered to establish a CAC mouse model. Moxibustion and KDM4D inhibitor 5-c-8HQ intervention were performed for 30 days after modeling was completed. IHC staining was used to observe the expression of the nuclear-associated antigen Ki67 (Ki67), proliferating cell nuclear antigen (PCNA), and IL-33 in the colon. The expression of colon KDM4D and β-Catenin was observed by immunofluorescence staining and RT‒qPCR. LC‒MS pseudotargeted metabolomic sequencing was used to semiquantitatively detect the expression levels of lipids.</p><p><strong>Results: </strong>Moxibustion inhibited the proliferation of colon tumors in CAC mice, improved histopathology, and reduced the expression of PCNA and Ki67 in the colon. Using kdm4d knockout technology, it was initially confirmed that kdm4d is a key gene affecting CAC tumor proliferation. The inhibition of colon tumor proliferation in CAC mice by moxibustion is associated with the suppression of abnormal activation of the colon KDM4D/β-Catenin signaling pathway. LC-MS-targeted metabolomics revealed abnormal lipid metabolism in the colons of CAC mice. Moxibustion may affect the cholinergic metabolism pathway in the colon of CAC mice and regulate lipids such as sphingomyelin SM (d18:1/26:0) and triacylglycerol TAG58:7 (18:0). After kdm4d knockout, lipid disorders in the colons of CAC mice were partially restored. The kdm4d gene may be involved in the mechanism underlying the effect of moxibustion on lipid metabolism in the CAC colon.</p><p><strong>Conclusions: </strong>Moxibustion inhibited the proliferation of colon tumors in CAC mice, inhibited the activation of the tumor-promoting signaling pathway KDM4D/β-Catenin, and improved lipid metabolism disorders in the colon, thus providing a promising strategy for the clinical adjuvant treatment of colorectal cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"173"},"PeriodicalIF":5.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic signatures in plasma circulating tumor DNA reveal treatment response and prognostic insights in mantel cell lymphoma.","authors":"Zhou Ouyang, Ruolan Zeng, Song Wang, Xiaoying Wu, Yajun Li, Yizi He, Caiqin Wang, Chen Xia, Qiuxiang Ou, Hua Bao, Wei Yang, Ling Xiao, Hui Zhou","doi":"10.1186/s12935-025-03789-9","DOIUrl":"https://doi.org/10.1186/s12935-025-03789-9","url":null,"abstract":"<p><strong>Background: </strong>Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin's lymphoma. The applicability of circulating tumor DNA (ctDNA) for predicting treatment response and prognosis in MCL remains underexplored.</p><p><strong>Methods: </strong>This study included 34 MCL patients receiving first-line chemoimmunotherapy. We assessed the ability of plasma ctDNA to detect tumor-specific genetic alterations and explored its potential as a noninvasive biomarker for treatment response and prognosis in MCL.</p><p><strong>Results: </strong>Commonly mutated genes in MCL included CCND1 (93.5%), ATM (48.4%), KMT2D (25.8%), and TP53 (25.8%). Subgroup analysis of tissue samples showed that CDKN2A mutations (P = 0.028), along with alterations in BCR and TCR signaling (P = 0.004) and the PI3K pathway (P = 0.008), were enriched in the blastoid subtype. ATM mutations (P = 0.041) were more prevalent in MIPI-low patients, while epigenetic chromatin remodeling pathway alterations (P = 0.028) were more common in MIPI-high patients. Plasma ctDNA demonstrated high sensitivity for detecting structural variants (96.6%), followed by mutations (71.3%) and copy number variants (30.0%). 75% of patients exhibited moderate-to-high concordance in detecting genomic variants between plasma and tissue samples. Pretreatment ctDNA levels exhibited high specificity in predicting clinical efficacy but had a suboptimal sensitivity of 68.2%. Higher ctDNA levels were significantly associated with shorter progression-free survival (PFS; P = 0.002) and overall survival (OS; P = 0.009). Additional ctDNA-based genetic features associated with shorter PFS included TP53 (P = 0.002), TRAF2 (P = 0.023), and SMARCA4 (P = 0.023) mutations, while TP53 (P = 0.006) and TERT (P = 0.031) mutations predicted shorter OS. Persistent positive ctDNA in post-treatment plasma samples indicated molecular relapse and poor prognosis, whereas undetectable ctDNA defined a subset of patients with favorable survival outcomes.</p><p><strong>Conclusions: </strong>This study identified plasma ctDNA as a promising biomarker that noninvasively captures tumor-derived genetic variants associated with treatment response and survival outcomes in MCL, highlighting the clinical value of ctDNA for diagnosis, recurrence prediction, and surveillance monitoring.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"172"},"PeriodicalIF":5.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The molecular subtyping and precision medicine in triple-negative breast cancer--- based on Fudan TNBC classification.","authors":"Lijuan Weng, Jianliang Zhou, Shenchao Guo, Nong Xu, Ruishuang Ma","doi":"10.1186/s12935-025-03799-7","DOIUrl":"https://doi.org/10.1186/s12935-025-03799-7","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"171"},"PeriodicalIF":5.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}