Cancer Cell International最新文献

{"title":"GADD45GIP1 promotes osteosarcoma progression by modulating RPL35 ubiquitination and alleviating endoplasmic reticulum stress via the PERK/eIF2α pathway.","authors":"Zhiqiang Li, Xiao Yu, Renjie Xu, Xiangxin Zhang, Jun Shen, Wei Xu","doi":"10.1186/s12935-025-03866-z","DOIUrl":"10.1186/s12935-025-03866-z","url":null,"abstract":"<p><p>Osteosarcoma, a common and aggressive bone tumor found in adolescents and children, is associated with a poor prognosis. The investigation of new molecular mechanisms is deemed vital for the development of innovative treatments. Transcriptomic survival analysis and single-cell RNA sequencing have identified seven highly expressed genes, including GADD45G interacting protein 1 (GADD45GIP1), that are linked to poor prognosis in patients with osteosarcoma. Tissue arrays, comprising 41 normal and 67 tumor cases, have further confirmed the high expression of GADD45GIP1 in osteosarcoma. Functional tests have demonstrated that the silencing of GADD45GIP1 significantly reduces the migration and proliferation of osteosarcoma cells in vitro and in vivo, while its overexpression has the opposite effect. Mechanistic studies have revealed 263 proteins that potentially interact with GADD45GIP1, identified through immunoprecipitation (IP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), with RPL35 ranking second among them. Cellular interference with RPL35 has been shown to activate the PERK-eIF2α pathway, increase endoplasmic reticulum (ER) stress, and affect the biological behavior of tumor cells. Additionally, the knockdown of GADD45GIP1 has led to a decrease in RPL35 protein stability and elevated polyubiquitination. Notably, the overexpression of RPL35 has counteracted the decrease in cell vitality induced by GADD45GIP1 knockdown. Thus, the high expression of GADD45GIP1 in osteosarcoma has been shown to inhibit the ubiquitin-mediated degradation of RPL35 and induce ER stress through the activation of the PERK-eIF2α pathway, thereby promoting the progression of osteosarcoma. This indicates that GADD45GIP1 serves as a key driver in the development of osteosarcoma and is a potential target for the prevention and therapy of osteosarcoma.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"242"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552378","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 GD3 ganglioside promotes cell growth, plasticity and chemotherapy resistance of human glioblastoma cancer stem cells.","authors":"Victoria Hein, Nathalie Baeza-Kallee, Raphaël Bergès, Nora Essakhi, Aurélie Soubéran, Carole Colin, Philippe Morando, Romain Appay, Thomas Graillon, Aurélie Tchoghandjian, Dominique Figarella-Branger, Emeline Tabouret","doi":"10.1186/s12935-025-03790-2","DOIUrl":"10.1186/s12935-025-03790-2","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma is the most aggressive primary brain tumour with no curative treatment and inevitable relapse. Therapeutic resistance is, at least, related to the presence of cancer stem-like cells in these tumours. Here, we aimed to demonstrate that the GD3 ganglioside was a relevant marker and actionable target for glioblastoma cancer stem-like cells.</p><p><strong>Methods: </strong>To this end, we used commercial glioblastoma cell lines, human glioblastoma samples, organotypic culture and xenografted mouse models to study GD3 antigen expression and consequences of its downregulation through a shRNA strategy targeting the ST8SIA1 mRNA which encodes the key enzyme for GD3 synthesis. We performed mono-dimensional Thin Layer Chromatography to analyse ganglioside composition of the glioblastoma samples and RNA-seq analyses to reveal oncogenic pathways and more specifically transcripts affected by ST8SIA1 silencing. Besides, we evaluated GD3 role in stemness of glioblastoma cancer cell, phenotype, microenvironment interaction, and invasion abilities.</p><p><strong>Results: </strong>We showed that GD3 is the main ganglioside in glioblastoma and that patient-derived cancer stem-like cell lines strongly expressed GD3. This GD3 + population decreased significantly after cell differentiation. GD3⁺ cells sorted from patient samples had stem-like cell properties: they were plastic, clonogenic, and tumorigenic after orthotopic engraftment. Silencing of ST8SIA1/GD3 was associated with a decrease in sphere size, self-renewal and migratory capacities and increased mouse survival. Moreover, increased temozolomide sensitivity was recorded. Finally, data from RNA-seq showed that silencing ST8SIA1/GD3 decreased oncogenic pathways and more specifically the expression of ADAMTS1 and IL33 transcripts.</p><p><strong>Conclusions: </strong>Taken together, our results suggest that GD3 ganglioside is essential for glioblastoma cancer stem-like cell properties, opening promising targeted therapeutic development.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"246"},"PeriodicalIF":5.3,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12224360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552384","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":"Efficacy and prognostic analysis of venetoclax combined with hypomethylating agents for induction therapy in acute myeloid leukemia: a multi-center real-world study on indication-specific stratification, molecular markers, and hematologic toxicities.","authors":"Leiming Xia, Mengni Qu, Ling Ge, Yingying Chen, Beibei Zhou, Ting Shi, Yang Liu, Min Ruan, Liang Xia, Jian Hong, Jianjun Li, Wei Qian, Yu Zhang, Lei Jiang, Yiming Zhao, Wanlu Tian, Zhenqi Huang, Fengbo Jin, Jian Ge, Mingzhen Yang, Qingshu Zeng","doi":"10.1186/s12935-025-03858-z","DOIUrl":"10.1186/s12935-025-03858-z","url":null,"abstract":"<p><p>The combination of venetoclax and hypomethylating agents (VEN + HMAs) has shown significant progress in treating acute myeloid leukemia (AML), especially for patients not suitable for intensive chemotherapy. However, outcomes for relapsed/refractory AML remain uncertain, and factors influencing VEN + HMAs efficacy are not yet conclusively determined. A retrospective analysis of 181 AML patients treated with VEN + HMAs from October 2020 to January 2024 revealed a CR rate of 39.2%, CR/CRi of 52.5%, ORR of 63.5%, and MRD negativity of 47.3% in patients receiving at least 7 days of treatment. Newly diagnosed patients had better outcomes than the relapsed/refractory group, with CEBPA or IDH1 mutations associated with better CR/CRi rates. Optimization of the treatment regimen with azacitidine may lead to higher CR/CRi rates and MRD negativity. Continuous VEN use over 21 days or maintaining a higher blood concentration may improve outcomes for newly diagnosed AML patients. Hematologic adverse events were common, but there were no significant differences in event rates or recovery times among different VEN treatment durations. VEN + HMAs shows promise in newly diagnosed AML but has limited efficacy in relapsed/refractory AML, indicating a need for more effective strategies. Genetic background, such as CEBPA or IDH1 mutations, influences VEN efficacy, with those mutations showing better CR/CRi rates. Choosing azacitidine for treatment and continuing VEN for over 21 days or at higher concentrations may lead to better responses in AML patients.Trial registration Clinical trial registration: we confirmed that our clinical trial has been officially registered with the Chinese Clinical Trial Registry (ChiCTR) and has been assigned the unique registration number: ChiCTR2400090821.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"241"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539057","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":"Skin melanoma cells produce diverse gelsolin (GSN) isoforms, which play non-redundant roles in cells' proliferation and motility.","authors":"Ewa Mazurkiewicz-Stanek, Aleksandra Makowiecka, Iryna Kopernyk, Michał Majkowski, Anna Boguszewska-Czubara, Tomasz Trombik, Paweł Karpiński, Piotr Donizy, Antonina J Mazur","doi":"10.1186/s12935-025-03876-x","DOIUrl":"10.1186/s12935-025-03876-x","url":null,"abstract":"<p><strong>Background: </strong>Skin melanoma is a malignant tumor that becomes increasingly difficult to treat when diagnosed late. Previously, we demonstrated that high levels of gelsolin (GSN) correlate with the advanced stages of cutaneous melanoma. GSN can be produced as various isoforms due to alternative splicing and differing start codon positions. To date, no studies have been conducted to determine whether GSN diverse isoforms are produced by melanoma cells in vivo and melanoma cell lines. Therefore, nothing is known about the role of specific GSN isoforms in skin melanoma biology.</p><p><strong>Methods: </strong>We applied immunocytochemical staining to melanoma tissue samples to analyze the localization of GSN production within tumor samples. Additionally, we utilized bioinformatics analysis of transcript levels coding for selected GSN isoforms in publicly available gene transcript databases. To investigate the role of these GSN isoforms, we used the melanoma A375 cell line with GSN knockout to restore the production of only one GSN isoform at a time in these cells. We evaluated the modified cells' ability to migrate, spread, and regulate actin polymerization. We also tested the cells growing on laminin 1, a significant component of the basement membrane, and the melanoma microenvironment.</p><p><strong>Results: </strong>We found that GSN expression produces three GSN isoforms in human melanoma cell lines: two cytosolic (B and C) and one secretory (A). Furthermore, we noted the presence of GSN both intracellularly and extracellularly in melanoma tumor samples, indicating that human melanoma cells produce diverse GSN isoforms in vivo. We discovered that cells producing GSN-A invade more efficiently, while cells producing GSN-C form the longest filipodia and migrate the best in 2D conditions. Both GSN-B and -C decrease the amount of filamentous actin. On the other hand, cells producing GSN-A and -B exhibit a lower proliferation rate. Finally, we observed that tumors formed by the clones expressing individual GSN isoforms do not grow in zebrafish embryos.</p><p><strong>Conclusions: </strong>Overall, we demonstrate that GSN isoforms are produced as a mixture in melanoma cells and are not redundant in their function. Therefore, to support the well-being of melanoma cells, a mixture of GSN isoforms must be produced.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"239"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144538975","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":"An EcDNA gene-based risk model and functional verification of a key ec-lncRNA AC016394.2 for prostate cancer.","authors":"JiangPing Qiu, Jiang Wu, Nan Zhou, Cong Lai, Xin Huang, Cheng Liu, XiaoQing Yuan, Kewei Xu","doi":"10.1186/s12935-025-03886-9","DOIUrl":"10.1186/s12935-025-03886-9","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer(PCa) ranks among the most frequently diagnosed malignancies in men. The progression and heterogeneity of tumors pose significant challenges to clinical prognosis and treatment strategies. Recently, extrachromosomal DNA(ecDNA) has emerged as a critical player in cancer biology, influencing tumor progression, metastasis, and resistance to therapy. Oncogenes and regulatory sequences carried on ecDNA(ecDNA genes) can significantly alter the biological characteristics of tumors and their clinical outcomes.</p><p><strong>Methods: </strong>In this study, we obtained ecDNA genes specifically expressed in PCa from the ECGA database. To construct a prognostic risk model for Biochemical Recurrence-Free Survival (BRFS), the two most common types of ecDNA genes which are protein-coding genes and long non-coding RNAs, were analyzed using Cox regression and LASSO regression techniques. Through KEGG/GO pathway enrichment analysis, we identified relevant pathways and analyzed the immune cell infiltration status. Functional assays, such as colony formation, CCK-8, migration, and invasion assays, were employed to assess the cellular functions of a key lncRNA AC016394.2.</p><p><strong>Results: </strong>Our analysis identified six key ecDNA lncRNAs(ec-lncRNAs), including the ec-lncRNA AC016394.2, with significant prognostic value in PCa. By employing our risk scoring model, patients were classified into high-risk and low-risk groups, revealing significant differences in their BRFS outcomes. The model demonstrated strong predictive accuracy and clinical relevance. The 1/3/5-year AUC of the model is close to 0.8, which is higher than most common clinical indicators such as Gleason score and TM staging. KEGG and GO pathway enrichment analyses revealed that the high-risk group was predominantly enriched in immune-related pathways. Additionally, immune cell infiltration analysis demonstrated notable differences in the distribution of specific immune cell populations between the high-risk and low-risk groups. Knockdown of AC016394.2 inhibited PCa cell proliferation, migration, and invasion.</p><p><strong>Conclusions: </strong>This study presents a novel ecDNA gene-based prognostic risk model for PCa, highlighting the functional importance of ec-lncRNA AC016394.2. These findings offer valuable insights into the biological role of ec-lncRNAs, highlighting their potential as targets for precision oncology and therapeutic intervention.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"240"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539056","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":"ACK1 condensates promote STAT5 signaling in lung squamous cell carcinoma.","authors":"Andong Liu, Xia Lu, Yanyang Song, Jiaying Pei, Ruozheng Wei","doi":"10.1186/s12935-025-03862-3","DOIUrl":"10.1186/s12935-025-03862-3","url":null,"abstract":"<p><strong>Background: </strong>ACK1, a non-receptor tyrosine kinase, phosphorylates various substrates involved in cancer progression. Its oncogenic activity is driven by gene amplification, mutations, and post-translational modifications. However, additional regulatory mechanisms that govern ACK1 activity remain to be fully understood. Liquid-liquid phase separation (LLPS) has emerged as a key mechanism of cellular compartmentalization, controlling the spatiotemporal dynamics of signaling pathways.</p><p><strong>Methods: </strong>Expression plasmids and corresponding mutants were generated using molecular cloning techniques. Protein expression and localization were assessed through western blotting, immunofluorescence, and confocal microscopy. LLPS properties were evaluated using time-lapse imaging, photobleaching, optoDroplet assays, and in vitro droplet formation assays. Cellular functions were examined through colony formation and wound-healing assays. STAT5 signaling activation was assessed by western blotting, co-immunoprecipitation (Co-IP), immunofluorescence, RNA sequencing (RNA-Seq), and Gene Set Enrichment Analysis (GSEA).</p><p><strong>Results: </strong>We demonstrate that ACK1 is frequently amplified and overexpressed in lung squamous cell carcinoma (LUSC). In LUSC cells, ACK1 undergoes LLPS, a process that depends on the intrinsically disordered region (IDR, 96-156 aa) but is independent of its kinase activity. We identify that the IDR induces droplet formation, with the 143-156 aa segment being essential for this activity. Furthermore, our data reveal that ACK1 phosphorylates STAT5 in LUSC cells. ACK1 condensates recruit the non-catalytic adaptors NCK1 and NCK2 and enhance STAT5 signaling. These condensates promote STAT5 nuclear localization and transcriptional activity, thereby facilitating LUSC cell growth and migration.</p><p><strong>Conclusions: </strong>Our findings highlight the crucial role of ACK1 condensates in oncogenic STAT5 signaling and suggest that targeting the formation of ACK1 condensates could serve as a potential therapeutic strategy for LUSC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"237"},"PeriodicalIF":5.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526514","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":"0.5ZnO@Cu5.4O nanoparticle for regulates the expression of GSDMB and targeted therapy of tumor.","authors":"Hao Zhang, Guoyan Liu","doi":"10.1186/s12935-025-03874-z","DOIUrl":"10.1186/s12935-025-03874-z","url":null,"abstract":"<p><p>GSDMB, a key protein in pyroptosis, is closely linked to various diseases. Nanomaterials can target and regulate specific pathways. Herein, we report a simple and efficient one-step method to develop multi-enzyme nanoparticles capable of suppressing GSDMB expression. 0.5ZnO@Cu5.4O can inhibit GSDMB, a capability that neither ZnO nor Cu5.4O possesses. ZnO@Cu5.4O with different ratios also exhibits varying inhibitory effects. The 0.5ZnO@Cu5.4O can be cleared quickly in vivo, ensuring biocompatibility. Additionally, 0.5ZnO@Cu5.4O significantly inhibits tumor progression, offering promising avenues for clinical cancer therapy, and the development of gene-regulating nanoparticles.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"238"},"PeriodicalIF":5.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526513","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":"Integrated transcriptome analysis and combinatorial machine learning to construct a homeostatic model of acetylation for ccRCC and validate the key gene GCNT4.","authors":"Baohua Zhu, Ziyang Mo, Yi Bao, Xinxin Gan, Linhui Wang","doi":"10.1186/s12935-025-03837-4","DOIUrl":"10.1186/s12935-025-03837-4","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors of the urinary system. Protein acetylation plays a key role in regulating cellular processes and cancer signaling pathways. This study explores the potential biological mechanisms of ccRCC from the perspective of acetylation.</p><p><strong>Methods: </strong>This study obtained RNA-seq data and clinical information of ccRCC from TCGA and ICGC, and single-cell RNA sequencing datasets from the GEO database. Ten machine learning algorithms and their 101 combinations were used to analyze the prognostic significance of acetylation-related differentially expressed genes (DEGs) and to construct a prognostic risk model. GSEA was used to analyze the enrichment of different signaling pathways in high-risk and low-risk groups, and the correlation between immune infiltration and risk scores was assessed. Finally, the function of the key gene GCNT4 was verified through cell experiments.</p><p><strong>Results: </strong>This study identified 84 acetylation-regulated key genes with significant expression differences between tumor and normal tissues, closely linked to patient prognosis. The LASSO + RSF combination model performed best, and the model could accurately predict patient prognosis. The survival of patients in the high-risk group was significantly worse than that in the low-risk group. High expression of GCNT4 was associated with better survival prognosis and was expressed at higher levels in normal tissues than tumor tissues. Overexpression of GCNT4 significantly inhibited the proliferation, invasion, and migration of renal cancer cells and may affect acetylation by regulating the levels of O-GlcNAc modification in cells.</p><p><strong>Conclusion: </strong>This study constructed a ccRCC acetylation homeostasis model via transcriptome analysis and machine learning, validating GCNT4 as a key gene. High expression of GCNT4 is associated with better survival prognosis and affects acetylation by regulating O-GlcNAc modification levels, inhibiting the proliferation and migration of renal cancer cells, providing a new potential target for the treatment of ccRCC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"236"},"PeriodicalIF":5.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494688","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":"Regulation of disease signaling by YOD1: potential implications for therapeutic strategies.","authors":"Jiawei Zhao, Xiaotong Guo, Houzhong Li, Yujing Chen, Jingjing Du, Juzheng Zhang, Jinfeng Gan, Peitao Wu, Siqi Chen, Xinwen Zhang, Jinfeng Yang, Jiamin Jin","doi":"10.1186/s12935-025-03881-0","DOIUrl":"10.1186/s12935-025-03881-0","url":null,"abstract":"","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"232"},"PeriodicalIF":5.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483240","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":"Prognostic value of a lncRNA signature in early-stage invasive breast cancer patients.","authors":"Rong Guo, Xiting Wang, Yinju Yang, Jiaying Zou, Ming Li, Zeying Li, Yuan Yan, Nan Lan, JianYun Nie, Yiyin Tang, Guojun Zhang","doi":"10.1186/s12935-025-03832-9","DOIUrl":"10.1186/s12935-025-03832-9","url":null,"abstract":"<p><strong>Background: </strong>Existing staging approaches fall short in precisely forecasting the likelihood of recurrence and survival outcomes among patients undergoing surgery for early-stage breast cancer (EBC). Our study hypothesized that multivariate long non-coding RNA (lncRNA) expression profiles, when systematically integrated into a composite model, may synergistically refine postoperative risk categorization and enhance prognostic forecasting precision in this patient cohort.</p><p><strong>Methods: </strong>For the discovery set, lncRNA expression profiling associated with breast cancer progression was discovered by analyzing the differential expression profiles in three paired primary breast cancer tumor tissues and liver metastases. We found 12 distinctially expressed lncRNAs. A total of 400 patients were consecutively recruited and randomized to either training group or validation group. We first confirmed the expression of these lncRNAs using qRT-PCR. Subsequently, employing the LASSO Cox regression model with five lncRNA features as covariates, we constructed a five-lncRNA signature. We then validated this signature in an independent cohort to assess its prognostic and predictive capabilities in disease-free survival (DFS) duration.</p><p><strong>Results: </strong>We constructed a classifier using the LASSO model, incorporating five specific lncRNAs: CBR3-AS1, HNF4A-AS1, LINC00622, LINC00993 and LINC00342. Utilizing this tool, we successfully stratified patients into two distinct categories: high- and low-risk groups. Significant differences were observed in both DFS and overall survival (OS) between the two groups. Within the initial patient cohort, significant differences of 5-year DFS was observed across high- and low-risk group (61.1% vs. 92.2%, HR 6.3, 95% CI 3.5-11.6; P < 0.001). The 5-year DFS rate was 72.9% and 85.4% for high- and low-risk group respectively in validation cohort (HR 2.6, 95% CI: 1.5-4.5; P = 0.001). The 5-lncRNA signature emerged as an independent prognostic indicator, demonstrating superior prognostic value compared to conventional clinicopathological risk factors.</p><p><strong>Conclusions: </strong>The integrated model combining 5-lncRNA molecular signature with clinical parameters demonstrates significant prognostic stratification capacity and therapeutic decision-making value in EBC management. It may help patients consult and personalize disease management.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"233"},"PeriodicalIF":5.3,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483239","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}