Cancer Cell International最新文献

{"title":"The emerging functions and clinical implications of circRNAs in acute myeloid leukaemia.","authors":"Shuiqing Liu, Xingyu Wan, Yang Gou, Wuchen Yang, Wei Xu, Yuxuan Du, Xiangui Peng, Xiaoqi Wang, Xi Zhang","doi":"10.1186/s12935-025-03772-4","DOIUrl":"https://doi.org/10.1186/s12935-025-03772-4","url":null,"abstract":"<p><p>Acute myeloid leukaemia (AML) is a prevalent haematologic malignancy characterized by significant heterogeneity. Despite the application of aggressive therapeutic approaches, AML remains associated with poor prognosis. Circular RNAs (circRNAs) constitute a unique class of single-stranded RNAs featuring covalently closed loop structures that are ubiquitous across species. These molecules perform crucial regulatory functions in the pathogenesis of various diseases through diverse mechanisms, including acting as miRNA sponges, interacting with DNA or proteins, and encoding functional proteins/polypeptides. Recently, numerous circRNAs have been confirmed to have aberrant expression patterns in AML patients. In particular, certain circRNAs are closely associated with specific clinicopathological characteristics and thus have great potential as diagnostic/prognostic biomarkers and therapeutic targets in AML. Herein, we systematically summarize the biogenesis, degradation, and functional mechanisms of circRNAs while highlighting their clinical relevance. We also outline a series of online databases and analytical tools available to facilitate circRNA research. Finally, we discuss the current challenges and future research priorities in this evolving field.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"167"},"PeriodicalIF":5.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960279","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":"Clinicopathological characterization of Switch/Sucrose-non-fermentable (Swi/Snf) complex (ARID1A, SMARCA2, SMARCA4)-deficient endocervical adenocarcinoma.","authors":"Chao Cao, Zi-Yun Wu, Wei Liao, Li-Jun Wei, Hao-Yu Liang, Xia Yang, Rong-Zhen Luo, Li-Li Liu","doi":"10.1186/s12935-025-03794-y","DOIUrl":"https://doi.org/10.1186/s12935-025-03794-y","url":null,"abstract":"<p><strong>Background: </strong>Subunits of the Switch/Sucrose-non-fermentable (Swi/Snf) complex, such as ARID1A, SMARCA4, SMARCA2, etc., have been implicated in the development of gynecologic cancers. However, their prevalence and clinical implications in endocervical adenocarcinoma (ECA) remain unclear. This study aimed to evaluate the expression of Swi/Snf complex subunits in ECA and characterize the clinicopathological and immune microenvironment features of Swi/Snf-deficient ECA.</p><p><strong>Methods: </strong>We evaluated 604 ECA using representative tissue microarrays, collected clinicopathologic data, reviewed histological features, and performed immunohistochemical staining for several Swi/Snf complex subunits, mismatch repair (MMR), immune cell markers, and immune checkpoint ligands proteins.</p><p><strong>Results: </strong>Among the 604 cases examined, five Swi/Snf subunit expression patterns were identified, including intact expression, deficient expression, 'checkerboard' expression, reduced expression, and heterogeneous expression. Deficiencies of ARID1A (3.97%, 24/604), SMARCA2 (2.32%,14/604), and SMARCA4 (1.49%, 9/604) were observed. Defining Swi/Snf deficiency as loss of any subunit, the overall deficiency rate was 5.96% (36/604). Swi/Snf-deficient ECA tended to advanced FIGO stage (III-IV, P = 0.041), larger tumor size (P < 0.001), deeper stromal invasion (≥ 1/3, P = 0.046), and higher lymph node metastasis rate (P = 0.037). Morphologically, Swi/Snf-deficient ECA displayed frequent poor differentiation (P = 0.001), medullary features (P < 0.001), high nuclear grade (P < 0.001), necrosis (P = 0.001), stromal tumor-infiltrating lymphocytes (sTILs, P < 0.001), peritumoral lymphocyte aggregation (P = 0.001), and tertiary lymphoid structures (TLS, P < 0.001). Immune subset analysis revealed significantly elevated densities of CD3⁺ T cells, CD8⁺ T cells, CD38⁺ plasma cells, CD56⁺ NK cells, CD68⁺ macrophages, and PD-1⁺ T cells in Swi/Snf-deficient ECA (P < 0.05). Swi/Snf-deficient ECA demonstrated higher PD-L1 combined positive score (CPS) positivity (P < 0.001), and was more frequently associated with mismatch repair deficiency (MMRD, P < 0.001). Survival analysis indicated shorter overall survival (median: 53 vs. 64.5 months, P = 0.0307) and disease-free survival (median: 52 vs. 60.5 months, P = 0.0228) in Swi/Snf-deficient ECA patients.</p><p><strong>Conclusions: </strong>Swi/Snf complex deficiency is rare but significantly associated with NHPVA, aggressive pathological features, immunologically activated phenotypes, and MMRD. Swi/Snf status evaluation may inform novel therapeutic strategies for ECA patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"170"},"PeriodicalIF":5.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966463","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":"Progress of mesenchymal stem cell-derived exosomes in targeted delivery of antitumor drugs.","authors":"Defa Huang, Wenlong Huang, Meijin Liu, Jie Chen, Dewang Xiao, Zongbo Peng, Haoquan He, Haibin Shen, Qing Jin, Linli Chen, Dingyu Rao, Minghong Zhao, Junyun Huang","doi":"10.1186/s12935-025-03795-x","DOIUrl":"https://doi.org/10.1186/s12935-025-03795-x","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are currently being used in clinical trials for the treatment of a wide range of diseases and have a wide range of applications in the fields of tissue engineering and regeneration. Exosomes are extracellular vesicles containing a variety of components such as proteins, nucleic acids and lipids, which are widely present in biological fluids and have the functions of participating in intercellular information transfer, immune response and tissue repair, and can also be used as carriers to target and deliver tumors to improve therapeutic effects. Mesenchymal stem cell-derived Exosomes (MSC-Exos), which have the advantages of low immunogenicity and high tumor homing ability, have attracted much attention in targeted drug delivery. Here, we review the current knowledge on the involvement of MSC-Exos in tumor progression and their potential as drug delivery systems in targeted therapies. It also discusses the advantages and prospects of MSC-Exos as a drug carrier and the challenges that still need to be overcome.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"169"},"PeriodicalIF":5.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961964","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":"Comprehensive pan-cancer analysis identified SLC16A3 as a potential prognostic and diagnostic biomarker.","authors":"Ping Yang, Jiayu Yin, Gongyin Zhang, Xiaofeng Li, Tongtong Chen, Wanying Zhao, Jinhai Tang, Li Lv, Xiupeng Lv","doi":"10.1186/s12935-025-03791-1","DOIUrl":"https://doi.org/10.1186/s12935-025-03791-1","url":null,"abstract":"<p><p>SLC16A3, belonging to the SLC16 gene family, is involved in the transportation of monocarboxylate. SLC16A family members play important roles in tumorigenesis, nonetheless, the specific involvement of SLC16A3 in tumor prognosis and diagnosis in human cancers remains unelucidated. This study dealt with the exploration of SLC16A3 expression in human pan-cancer and its significance regarding disease prognosis. For this investigation, the mRNA expression data of SLC16A3 were acquired from the TCGA and the GTEx datasets. The Kaplan-Meier plots, univariate Cox regression, and the ROC curve were employed for assessing the prognostic and diagnostic significance of SLC16A3 in pan-cancer. Furthermore, the cBioPortal database was used to analyze the SLC16A3 genomic alterations. Moreover, the association of the infiltration of immune cells and immune checkpoint genes with SLC16A3 was analyzed by the TIMER database. Gene Ontology and KEGG pathway analysis were employed to explore the function of SLC16A3 in pan-cancer. The resulting data demonstrated that SLC16A3 mRNA expression was overexpressed in most cancers and its protein expression was also high across diverse cancer types. Moreover, upregulated SLC16A3 expression was linked to poor OS and PFI of certain cancers. Cox regression analysis further indicated that SLC16A3 is a risk factor for patients with PAAD, CESC, LUSC, LUAD, CHOL, LGG, MESO, and OSCC. The ROC curve revealed that SLC16A3 exhibited a high accuracy (AUC > 0.9) in BRCA, CHOL, ESCA, GBM, and KIRC prediction. Moreover, the acquired data indicated that in pan-cancer, the SLC16A3 expression exhibited correlations with immune checkpoint genes and immune cells. These findings collectively suggest that SLC16A3 holds promise as a biomarker for diagnostic and prognostic purposes in pan-cancer.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"168"},"PeriodicalIF":5.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980816","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":"Establishment and evaluation cuproptosis-related gene signature for predicting the prognosis and immunotherapy response of hepatocellular carcinoma.","authors":"Shuo Wang, Xinzi Xue, Hongyan Bai, Junwen Qi, Sujuan Fei, Bei Miao","doi":"10.1186/s12935-025-03688-z","DOIUrl":"https://doi.org/10.1186/s12935-025-03688-z","url":null,"abstract":"<p><strong>Background: </strong>This study aims to develop a novel cuproptosis-related model through bioinformatics analysis, providing new insights into HCC classification. It also explores the correlation between the cuproptosis-related risk score and factors such as prognosis, tumor mutation burden (TMB), biological function, tumor microenvironment (TME), and immune efficacy.</p><p><strong>Methods: </strong>We performed unsupervised clustering of cuproptosis-related gene expression profiles from TCGA and GEO to identify molecular subtypes and differentially expressed genes. Prognostic models were constructed using univariate, Lasso, and multivariate Cox regression analyses. HCC patients were classified into high-risk and low-risk subgroups, and the model's prognostic value was assessed through survival analysis, ROC curves, and nomograms. Immune checkpoint, drug sensitivity, and IPS were used to evaluate immunotherapy response. The model's predictive ability was further validated with the ICGC database and IMvigor210 cohort. Finally, key gene expression and biological functions were validated in human tissues and HCC cell lines.</p><p><strong>Results: </strong>The cuproptosis-related gene risk score model (CRGRM), based on GMPS, DNAJC6, BAMBI, MPZL2, ASPHD1, IL7R, EPO, BBOX1, and CXCL9, independently predicted HCC prognosis and immune response. Clinical correlation and ROC curve analysis demonstrated its accuracy in predicting 0.5-, 1-, 3-, and 5-year survival. The risk score also strongly correlates with immunotherapy response and serves as a reliable treatment predictor. Drug sensitivity analysis revealed that the low-risk group was more sensitive to dasatinib, imatinib, and gefitinib. In vitro, BAMBI knockdown significantly inhibited HCC cell proliferation and metastasis.</p><p><strong>Conclusions: </strong>This model demonstrates potential in predicting prognosis and immunotherapy response, providing insights into personalized treatment strategies for HCC. Additionally, our study suggests that BAMBI may serve as a novel biomarker and potential therapeutic target for HCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"166"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965960","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 human microbiome: redefining cancer pathogenesis and therapy.","authors":"Yogita K Adlakha, Ravindresh Chhabra","doi":"10.1186/s12935-025-03787-x","DOIUrl":"https://doi.org/10.1186/s12935-025-03787-x","url":null,"abstract":"<p><p>The human microbiome has always been an important determinant of health and recently, its role has also been described in cancer. The altered microbiome could aid cancer progression, modulate chemoresistance and significantly alter drug efficacy. The broad implications of microbes in cancer have prompted researchers to investigate the microbe-cancer axis and identify whether modifying the microbiome could sensitize cancer cells for therapy and improve the survival outcome of cancer patients. The preclinical data has shown that enhancing the number of specific microbial species could restore the patients' response to cancer drugs and the microbial biomarkers may play a vital role in cancer diagnostics. The elucidation of detailed interactions of the human microbiota with cancer would not only help identify the novel drug targets but would also enhance the efficacy of existing drugs. The field exploring the emerging roles of microbiome in cancer is at a nascent stage and an in-depth scientific perspective on this topic would make it more accessible to a wider audience. In this review, we discuss the scientific evidence connecting the human microbiome to the origin and progression of cancer. We also discuss the potential mechanisms by which microbiota affects initiation of cancer, metastasis and chemoresistance. We highlight the significance of the microbiome in therapeutic outcome and evaluate the potential of microbe-based cancer therapy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"165"},"PeriodicalIF":5.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976267","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":"Characterization and comparative profiling of piRNAs in serum biopsies of pediatric Wilms tumor patients.","authors":"Fatma S Mohamed, Deena Jalal, Youssef M Fadel, Samir F El-Mashtoly, Wael Z Khaled, Ahmed A Sayed, Mohamed A Ghazy","doi":"10.1186/s12935-025-03780-4","DOIUrl":"https://doi.org/10.1186/s12935-025-03780-4","url":null,"abstract":"<p><p>Piwi-interacting RNAs (piRNAs) are small non-coding RNAs involved in transposon silencing and linked to cancer progression. However, their role in Wilms tumors (WT) remains unexplored. We conducted a thorough analysis and characterization of piRNAs in serum liquid biopsies of WT patients. Our study examined their expression patterns and functional annotations related to WT pathogenesis, as well as their clinical potential for diagnosis and monitoring. We identified 307 piRNAs expressed in WT serum samples, with 4% classified as repeat-related and 96% as non-repeat-related. The most abundant repeat-related piRNAs originated from LINEs retrotransposon, while tRNA-derived piRNAs were the most prevalent among non-repeat-related piRNAs. Furthermore, a distinct profile of 34 piRNAs showed significant differential expression in WT patients compared to healthy controls-22 downregulated and 12 upregulated. The target genes of differentially expressed piRNAs exhibited significant enrichment in biological pathways related to cytokine activity, inflammatory responses, TGF-beta signaling, p38 MAPK, and ErbB signaling. These genes are also involved in DNA damage response, DNA methylation, cell cycle regulation, as well as kidney development and function. Low expression levels of several piRNAs, especially piR-hsa-1,913,711, piR-hsa-28,190, piR-hsa-28,849, piR-hsa-28,848, and piR-hsa-28,318, showed significant diagnostic potential as non-invasive biomarkers for WT (AUC > 0.8, p < 0.05). Their expression levels also significantly correlated with adverse pathological features, including metastasis, anaplasia, and bilateral WT development. In conclusion, non-transposon-related piRNAs may serve as reliable biomarkers for WT and possess potential non-germline functions, particularly in regulating DNA methylation, cell growth, immune responses, and immune responses. Further studies are warranted to elucidate their functional significance.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"163"},"PeriodicalIF":5.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980556","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":"USP24 promotes hepatocellular carcinoma progression by deubiquitinating and stabilizing YAP1.","authors":"Huizhuang Shan, Jiaguo Yuan, Luhua Xian, Wenmin Li, Yanfen Ge, Lei Zhang, Ting Lin, Mingwei Lan, Junru Liu, Yanfei Luo, Yingli Wu, Xinhua Xiao","doi":"10.1186/s12935-025-03796-w","DOIUrl":"https://doi.org/10.1186/s12935-025-03796-w","url":null,"abstract":"<p><p>Yes-associated protein 1 (YAP1) plays a pivotal role in promoting the progression of hepatocellular carcinoma (HCC). Emerging evidence shows that inducing YAP1 degradation represents a promising strategy. Here, we identified USP24 as a bona fide deubiquitinating enzyme for YAP1. USP24 directly interacts with and deubiquitinates YAP1, thereby stabilizing YAP1 protein levels. Clinically, USP24 was significantly upregulated in HCC tissues and correlated with poor patient prognosis. Depletion of USP24 significantly suppressed the proliferation of HCC cells in vitro, which could be rescued by restoration of YAP1. Consistent with these findings, USP24 knockdown inhibited tumor growth in a xenograft mouse model. Overall, our study reveals that the USP24/YAP1 axis plays a critical role in the malignant progression of HCC, thus providing rationale for potential therapeutic interventions for YAP1-driven HCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"164"},"PeriodicalIF":5.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959267","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":"YEATS2: a novel cancer epigenetic reader and potential therapeutic target.","authors":"Kangkang Ji, Guoping Chen, Yan Wang, Yunyi Li, Jian Chen, Mingqian Feng","doi":"10.1186/s12935-025-03797-9","DOIUrl":"https://doi.org/10.1186/s12935-025-03797-9","url":null,"abstract":"<p><p>YEATS2, an evolutionarily conserved reader of histone acylation marks (H3K27ac, H3K27cr, H3K27bz), functions as a central oncogenic driver in diverse cancers, including non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC). Its structurally plastic YEATS domain bridges acyl-CoA metabolism to chromatin remodeling, amplifying transcription of survival genes such as MYC, BCL2, and PD-L1. YEATS2 orchestrates malignancy-specific programs-sustaining ribosome biogenesis in NSCLC through ATAC complex recruitment, enhancing NF-κB-dependent immune evasion in PDAC, and activating PI3K/AKT-driven metabolic rewiring in HCC. Structural studies demonstrate a unique aromatic cage architecture that selectively engages diverse acylated histones. Although pyrazolopyridine-based inhibitors targeting the YEATS domain show preclinical efficacy, developing isoform-selective agents remains challenging. Clinically, YEATS2 overexpression correlates with therapy resistance and may synergize with immune checkpoint blockade. This review integrates mechanistic insights into the role of YEATS2 in epigenetic regulation, evaluates its therapeutic potential, and proposes future directions: elucidating full-length complex topologies, mapping synthetic lethal interactors, and optimizing selective inhibitors. Disrupting YEATS2-mediated epigenetic adaptation presents novel opportunities for precision cancer therapy.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"162"},"PeriodicalIF":5.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982730","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":"Liquid biopsy-derived extracellular vesicle protein biomarkers for diagnosis and prognostic assessment of lung squamous cell carcinoma.","authors":"Sheng Ma, Na Zhao, Xin Dong, Yaru Wang, Lei Song, Ruiqi Zheng, Xiaochen Zhi, Congcong Ma, Shujun Cheng, Jie Li, Yutao Liu, Ting Xiao","doi":"10.1186/s12935-025-03792-0","DOIUrl":"https://doi.org/10.1186/s12935-025-03792-0","url":null,"abstract":"<p><strong>Background: </strong>For patients with nodules detected in imaging that are indeterminate for malignancy, achieving accurate, early, and non-invasive diagnosis of Lung Squamous Cell Carcinoma (LUSC) remains a significant challenge. Therefore, we aimed to establish diagnostic and prognostic models by identifying plasma extracellular vesicles (EVs) associated protein biomarkers specific to LUSC.</p><p><strong>Methods: </strong>This study employed a novel nanomaterial, NaY, for the enrichment of EVs from plasma. Validation was conducted through transmission electron microscopy, nanoparticle tracking analyses, and Western blotting. Machine learning algorithms were utilized to compute protein biomarkers associated with LUSC and establish a diagnostic model. Additionally, a prognostic prediction model for LUSC was developed using a combination of 101 machine learning algorithms. Risk scoring of patients was performed to explore the underlying reasons for prognostic differences between high and low-risk groups.</p><p><strong>Results: </strong>The results of three experiments demonstrate that the new nanomaterial NaY effectively enriches EVs from plasma. Analysis of the enriched profile reveals pathways related to glycolysis/gluconeogenesis and carbon metabolism enriched in plasma EVs of LUSC patients. Thirty-eight LSCC-related EV biomarkers were identified, from which five proteins (TUBB3, RPS7, RPLP1, KRT2, and VTN) were selected to establish a diagnostic model distinguishing between benign and LUSC nodules. The diagnostic efficacy of RPS7 and VTN was further validated in independent samples using ELISA experiments. Furthermore, DPYD, GALK1, CDC23, UBE2L3, RHEB, and PSME1 were determined as potential prognostic biomarkers. Subsequently, risk scores were computed for each sample, classifying all patients into high and low-risk groups. Enrichment analysis revealed that EVs from the high-risk group contained proteins promoting cell proliferation and invasion, while those from the low-risk group were enriched in immune-related protein biomarkers.</p><p><strong>Conclusions: </strong>The novel nanomaterial NaY effectively enriches EVs from plasma. Utilizing plasma EV biomarkers, the diagnostic model demonstrates strong discriminative ability between benign and malignant pulmonary nodules in patients.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"161"},"PeriodicalIF":5.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977025","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}