Oncology Research最新文献

{"title":"Retraction: Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway.","authors":"","doi":"10.32604/or.2025.073035","DOIUrl":"https://doi.org/10.32604/or.2025.073035","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504017X14944585873631.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 10","pages":"3159"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3<b>β</b>-Hydroxysterol <b>Δ</b>24-Reductase Promotes Ovarian Cancer Progression by Activating the TGF-<b>β</b>1/Smad2/3 Signaling Pathway.","authors":"Wenjing Liao, Liaodi Wang, Zhen Huang, Ziyu Zou, Yimin Liu, Haoyue Liu, Zhaoning Duan, Liangdan Tang","doi":"10.32604/or.2025.065451","DOIUrl":"10.32604/or.2025.065451","url":null,"abstract":"<p><strong>Objectives: </strong>Ovarian cancer (OC) is a highly heterogeneous disease characterized by high metastatic potential and frequent recurrence. 3β-hydroxysterol Δ24-reductase (DHCR24) is closely associated with the progression of various malignant tumors, but its role in OC remains unexplored. This study is the first to systematically investigate the function of DHCR24 in OC and elucidate its mechanism in promoting OC progression, providing novel theoretical insights for targeted therapy.</p><p><strong>Methods: </strong>The expression of DHCR24 was evaluated in tissues using bioinformatics and clinical data; the impact of DHCR24 on the malignant behavior of OC was assessed through <i>in vivo</i> and <i>in vitro</i> experiments; and the mechanism by which DHCR24 functions in OC was preliminarily explored using sequencing and rescue experiments. Statistical analysis was conducted using the chi-square test, <i>t</i>-test, and one-way ANOVA.</p><p><strong>Results: </strong>Database, clinical data, and immunohistochemical (IHC) analyses demonstrated that DHCR24 is upregulated in OC and correlates with poor outcomes. <i>In vitro</i> experiments indicated that DHCR24 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition in OC cells. The addition of a DHCR24 inhibitor suppressed the malignant behavior of OC cells. The nude mouse tumor formation experiment demonstrated that inhibiting DHCR24 suppresses the <i>in vivo</i> growth of OC cells. Further experiments showed that DHCR24 promotes the malignant behavior of OC cells, correlating with the regulation of the transforming growth factor beta (TGF-β) signaling pathway. All the above experiments showed statistical significance.</p><p><strong>Conclusion: </strong>DHCR24 contributes to ovarian cancer progression by upregulating the TGF-β1 pathway, highlighting its potential as a therapeutic target in ovarian cancer.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 10","pages":"3041-3064"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical Chemotherapy for Ocular Surface Squamous Neoplasia: A Review of Adverse Effects and Their Clinical Management.","authors":"Lina Corgiolu, Giuseppe Giannaccare, Alberto Cuccu","doi":"10.32604/or.2025.067221","DOIUrl":"10.32604/or.2025.067221","url":null,"abstract":"<p><p>Topical chemotherapy is increasingly used to treat ocular surface tumors as a primary therapy and an adjuvant treatment after surgical excision. The most employed topical agents include mitomycin C (MMC), 5-fluorouracil (5-FU), and interferon alpha-2b (IFNα2b), each with distinct mechanisms of action, efficacy profiles, and toxicity risks. Although these agents offer effective tumor control and allow for a non-invasive approach in many cases, ocular surface complications requiring medical or surgical management can occur. This summarizes the adverse effect and outilines practical strategies for their prevention and treatment. MMC is the most potent agent but also the most toxic, with reported complications such as limbal stem cell deficiency, punctal stenosis, and persistent epithelial defects. 5-FU demonstrates a more favorable safety profile, although rare cases of corneal ulceration have been described. IFNα2b is well tolerated and associated primarily with mild, reversible reactions. The choice of the proper agent should be tailored according to patient's clinical presentation, ocular surface status, and ability to adhere to therapy and follow-up. Timely recognition and management of complications are essential to minimize long-term sequelae. Reliance on compounded formulations highlights the need for stable, standardized, and commercially available topical agents specifically designed for ocular use to ensure safety, reproducibility, and global accessibility.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 10","pages":"2725-2740"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a Novel Oxidative Stress-Based Molecular Classification and Treatment Vulnerabilities in WHO Grade 2/3 Meningiomas.","authors":"Xiao-Xiao Luo, Bi Peng, Jian-Hua Wang, Guang-Yuan Hu, Xiang-Lin Yuan, Guo-Xian Long","doi":"10.32604/or.2025.066308","DOIUrl":"10.32604/or.2025.066308","url":null,"abstract":"<p><strong>Objective: </strong>The World Health Organization (WHO) grading based on histopathology cannot always accurately predict tumor behavior of meningiomas. To overcome the limitations of the WHO grading, the study aims to propose a novel oxidative stress-based molecular classification for WHO grade 2/3 meningiomas.</p><p><strong>Methods: </strong>Differentially expressed oxidative stress-related genes were analyzed between 86 WHO grade 1 (low grade) meningiomas and 99 grade 2/3 (high grade) meningiomas. An oxidative stress-based molecular classification was developed in high-grade meningiomas through consensus clustering analysis. Immune microenvironment features, responses to immunotherapy and chemotherapy, and targeted drugs were evaluated. Three machine learning models: logistic regression, support vector machine, and random forest, were built for differentiating the classification. Key oxidative stress-related genes were verified in human meningeal cells (HMC) and two meningioma cells (CH-157MN and IOMM-Lee) via reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. After knockdown of Forkhead Box M1 (FOXM1) or Prion Protein (PRNP), cell growth, migration, and reactive oxygen species (ROS) levels were measured through cell counting kit-8 (CCK-8), transwell, and immunofluorescence, respectively.</p><p><strong>Results: </strong>We classified high-grade meningiomas into two oxidative stress-based clusters, termed cluster 1 and cluster 2. Cluster 1 exhibited higher infiltrations of immune and stromal cells and higher expression of classic immune checkpoints: Cluster of Differentiation 86 (CD86), Programmed Cell Death 1 (PDCD1), and Leukocyte-Associated Immunoglobulin-Like Receptor 1 (LAIR1), indicating that cluster 1 meningiomas might respond to immunotherapy. Drug sensitivity was heterogeneous between the two clusters. Three classifiers were established, which could accurately differentiate this molecular classification. FOXM1 and PRNP were experimentally evidenced to be highly expressed in meningioma cells, and their knockdown hindered cell growth and migration and triggered ROS accumulation.</p><p><strong>Conclusion: </strong>In summary, our findings established a novel oxidative stress-based molecular classification and identified potential treatment vulnerabilities in high-grade meningiomas, which might assist personalized clinical management.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 10","pages":"2903-2921"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Silencing of lncRNA CCDC26 Restrains the Growth and Migration of Glioma Cells <i>In Vitro</i> and <i>In Vivo</i> via Targeting miR-203.","authors":"","doi":"10.32604/or.2025.073033","DOIUrl":"https://doi.org/10.32604/or.2025.073033","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504017X14965095236521.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 10","pages":"3157"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYP19A1 Silencing Inhibits Cell Proliferation and Endoplasmic Reticulum Stress in Stomach Adenocarcinoma.","authors":"Yi Jin, Zexing Shan, Fan Yang, Xinwen Fan, Jie Lin, Zeqing Huang, Xudong Zhu","doi":"10.32604/or.2025.062250","DOIUrl":"10.32604/or.2025.062250","url":null,"abstract":"<p><strong>Background: </strong>As a major histopathological subtype of gastric cancer (GC), stomach adenocarcinoma (STAD) is an important malignant tumor in the digestive system. Increasing evidence also indicates that endoplasmic reticulum (ER) stress plays a pivotal role in the pathogenesis and progression of GC. Therefore, this study aims to screen and identify vital ER stress-related genes that could contribute to the malignant development and poor prognosis for STAD.</p><p><strong>Methods: </strong>A novel ER stress-related risk score signature was developed employing machine learning techniques. Then, a prognostic prediction nomogram was also built based on the clinicopathological characteristics and the risk score signature. The tumor immune microenvironment characteristics and pathway enrichment analysis in different risk groups were also explored. Furthermore, through the single-cell RNA sequencing (scRNA-seq) analysis, the study highlighted Cytochrome P450 Family 19 Subfamily A Member 1 (CYP19A1) as the pivotal research target and detected its effect on cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and the expression of ER stress-related genes by RT-qPCR in STAD.</p><p><strong>Results: </strong>Based on the evaluation of five screened key ER stress-related genes (<i>AKR1B1</i>, <i>SERPINE1</i>, <i>ADCYAP1</i>, <i>MATN3</i>, <i>CYP19A1</i>), our ER stress-related risk score signature offers a novel approach for assessing STAD prognosis hazards. The novel prognostic prediction nomogram based on the signature also accurately predicted the survival outcomes of patients with STAD. Furthermore, the expression of <i>CYP19A1</i> is significantly higher in STAD tissues than in normal tissues. High expression of <i>CYP19A1</i> was related to a poor survival outcome for patients with STAD. Besides, compared to normal gastric epithelial cells, the expression of <i>CYP19A1</i> was significantly higher in STAD cell lines. Silencing the expression of <i>CYP19A1</i> significantly inhibited the cell proliferation ability and decreased the expression of ER stress-related genes, including <i>ATF4</i>, <i>DDIT3</i> and <i>XBP1</i> in STAD.</p><p><strong>Conclusions: </strong>In conclusion, our study developed a novel prognosis prediction signature and identified the novel diagnostic and therapeutic target CYP19A1 for patients with STAD.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 10","pages":"2937-2960"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and Characterization of Novel IKZF1/3 Glue Degraders against Multiple Hematological Cancer Cell Lines.","authors":"Ting Wei, Pengli Wei, Yalei Wang, Yaqiu Mao, Jian Yan, Xiaotong Hu, Zhenze Qi, Xu Cai, Changkai Jia, Zhiyuan Zhao, Bingkun Li, Min Qiao, Yaxin Zou, Tingting Yang, Shiyang Sun, Xuesong Feng, Pengyun Li, Hongzhou Shang, Zhibing Zheng","doi":"10.32604/or.2025.065123","DOIUrl":"10.32604/or.2025.065123","url":null,"abstract":"<p><strong>Objectives: </strong>Immunomodulatory drugs (IMiDs), functioning as molecular glue degraders, have been approved for treating various hematological malignancies; however, the inevitable acquired drug resistance resulting from their skeletal similarity and hematological toxicities poses significant obstacles to their clinical treatment. The study aimed to develop degraders with potent efficiency and low toxicity.</p><p><strong>Methods: </strong>Phenotypic profiling, elaborate structure-activity relationships (SAR), rational drug design and degradation profiles investigations, quantitative proteomics analysis and cell-based functional studies, and pharmacokinetic studies were conducted to develop more potent degraders.</p><p><strong>Results: </strong>This study developed novel CRBN-binding moieties through methylene deletion in lenalidomide's isoindole core. Lead compounds MGD-A7 and MGD-C9 demonstrated superior antiproliferative efficacy vs. IMiDs, with submicromolar potency. MGD-A7 and MGD-C9 significantly and selectively induced the degradation of Ikaros Family Zinc Finger Proteins 1 and 3 (IKZF1/3) with nanomolar potency via a CRBN-dependent pathway. Mechanistically, MGD-A7 and MGD-C9 dramatically induced cell apoptosis and G1 cell cycle arrest and MGD-C9 exhibited favorable pharmacokinetic properties <i>in vivo</i>. Furthermore, MGD-C9 exhibited significant synergistic effects with standard-of-care agents in various hematological malignancy cells.</p><p><strong>Conclusions: </strong>These results indicate that MGD-C9 could act as a highly effective CRBN ligand and is expected to become a candidate drug for the treatment of hematological malignancies.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 10","pages":"2981-3006"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Breast Cancer Cell Proliferation by 9-Hydroxycamptothecin-Loaded Zeolitic Imidazolate Nanoparticles.","authors":"Chuansheng Yang, Xiaoling Zhou, Ling Luo, Zirun Luo, Kaiming Fan, Chenglai Xia","doi":"10.32604/or.2025.066058","DOIUrl":"10.32604/or.2025.066058","url":null,"abstract":"<p><strong>Objectives: </strong>Novel drug delivery systems have been designed to enhance local drug concentrations while reducing side effects conducive to improved breast cancer treatment outcomes. This study aimed to identify the anti-cancer function of zeolite imidazole ester-based material loaded with camptothecin nanoparticles.</p><p><strong>Methods: </strong>We utilized a zeolitic imidazolate backbone material to fabricate 9-hydroxycamptothecin nanoparticles and investigated their impact on breast cancer cell proliferation. Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed changes in the carrier skeleton of the loaded 9-hydroxyl camptothecin, characterized by a reduction in surface smoothness, accompanied by slight collapses and folds on the particle surface. Notably, we detected vibration of the benzene ring in the 9-hydroxycamptothecin structure within the nanoparticles. Cell proliferation was tested by CCK-8. Protein expression was measured by Western blot. The efficacy of nanoparticles was evaluated by animal experiments.</p><p><strong>Results: </strong>In this study, we utilized a zeolitic imidazolate backbone material to fabricate 9-hydroxycamptothecin (9-HCPT) nanoparticles and investigated their impact on breast cancer cell proliferation. Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed changes in the carrier skeleton of the loaded 9-hydroxyl camptothecin, characterized by a reduction in surface smoothness, accompanied by slight collapses and folds on the particle surface. Notably, we detected vibration of the benzene ring in the 9-HCPT structure within the nanoparticles. Using the CCK-8 method, we evaluated the inhibitory effect of these nanoparticles on breast cancer cells and observed a significant reduction in the cytotoxicity of camptothecin (CPT) when incorporated into the zeolite imidazole ester skeleton material. Immunoblot analysis showed upregulation of cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), and NF-κB-p65 in response to the nanoparticles. These results showed that our nanoparticles might be a useful drug delivery strategy to overcome breast cancer drug resistance.</p><p><strong>Conclusion: </strong>The findings of this study suggest that nanoparticles loaded with CPT and formed from zeolite imidazole ester backbone material possess immune-enhancing properties that could suppress breast cancer progression. Accordingly, these nanoparticles hold promise as potential lead compounds for combined immunotherapy in breast cancer treatment.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 10","pages":"3065-3076"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAMK2B Impacts the Proliferation, Invasion, and Migration of Glioma Cells via the Ras/Raf/MEK/ERK Signaling Pathway.","authors":"Shiyang Zhang, Jingchen Li, Qianxu Jin, Siyu Zhu, Hongshan Yan, Yizheng Wang, Zihan Song, Liqiang Liu","doi":"10.32604/or.2025.064300","DOIUrl":"10.32604/or.2025.064300","url":null,"abstract":"<p><strong>Background: </strong>Glioma is the most common tumor of the central nervous system with a poor prognosis. This study aims to explore the role of calcium/calmodulin-dependent protein kinase IIβ (CAMK2B) in regulating the malignant progression of glioma cells, as well as the molecular mechanisms underlying these malignant behaviors.</p><p><strong>Methods: </strong>The correlation between CAMK2B expression in gliomas and patient prognosis was analyzed using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blot. Furthermore, the study explored the role of CAMK2B in glioma cell proliferation, invasion, and migration using cell counting kit-8 (CCK-8), 5-Ethynyl-2^'-deoxyuridine (EdU), wound healing, transwell, and <i>in vivo</i> tumor xenograft assays.</p><p><strong>Result: </strong>Patients with high CAMK2B expression exhibited significantly better prognostic outcomes compared to those with low expression levels. Furthermore, CAMK2B expression was significantly lower in glioma tissues and cells compared to both normal brain tissue and human astrocyte cell lines. Notably, overexpression of CAMK2B in glioma cells led to an approximate 40% reduction in proliferative capacity and a 60-70% decrease in invasive and migratory abilities, compared to control glioma cells. These differences were statistically significant at <i>p</i> < 0.05. Conversely, knockdown of CAMK2B using siRNA-CAMK2B significantly enhanced the proliferative, invasive, and migratory capabilities of glioma cells in both <i>in vitro</i> and <i>in vivo</i> settings, enhancing these abilities by 1.5 to 3 times. Notably, these effects were reversed through the application of the Rat Sarcoma viral oncogene homolog (Ras) pathway inhibitor, Salirasib. Western blot analysis revealed that knockdown of CAMK2B led to activation of the Ras/Rapidly Accelerated Fibrosarcoma (Raf)/Mitogen-activated protein kinase kinase (MEK)/Extracellular signal-regulated kinase (ERK) signaling pathway in glioma cell lines, whereas overexpression of CAMK2B resulted in the suppression of this pathway.</p><p><strong>Conclusion: </strong>CAMK2B inhibits glioma proliferation, invasion, and migration through the Ras/Raf/MEK/ERK signaling pathway.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 10","pages":"2961-2979"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NLR Risk Score for Predicting Patient Prognosis in Hepatocellular Carcinoma and Identification of Oncogenic Role of NLRP5 in Hepatocellular Carcinoma.","authors":"Mingyang Tang, Shengfu He, Bao Meng, Qingyue Zhang, Chengcheng Li, Yating Sun, Weijie Sun, Cui Wang, Qingxiang Kong, Yanyan Liu, Lifen Hu, Yufeng Gao, Qinxiu Xie, Jiabin Li, Ting Wu","doi":"10.32604/or.2025.067065","DOIUrl":"10.32604/or.2025.067065","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths. The Nod-like receptor (NLR) family is involved in innate immunity and tumor progression, but its role in HCC remains unclear. This study aimed to evaluate the prognostic value and biological function of NLR genes in HCC.</p><p><strong>Methods: </strong>Transcriptomic and clinical data from The Cancer Genome Atlas were analyzed using nonnegative matrix factorization (NMF) to classify HCC into molecular subtypes. Differentially expressed genes were used to build an NLR-based prognostic model (NLR_score) through univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression. Predictive performance and correlation with chemotherapy sensitivity were assessed. NLR family pyrin domain containing 5 (NLRP5) was identified as a key oncogene and validated via <i>in vitro</i> assays, including cell counting kit-8 (CCK-8), colony formation, transwell, and flow cytometry <i>in vivo</i> xenograft models.</p><p><strong>Results: </strong>The two NMF-defined subtypes showed distinct survival outcomes. The NLR_score reliably predicted prognosis and was associated with sensitivity to six chemotherapeutic drugs. NLRP5 knockdown suppressed HCC cell proliferation, migration, and invasion <i>in vitro</i> and reduced tumor growth <i>in vivo</i>. Mechanistically, NLRP5 modulated the p53 signaling pathway, influencing cell cycle and apoptosis.</p><p><strong>Conclusion: </strong>This study developed an NLR-based prognostic model that effectively stratifies HCC patients by survival risk. NLRP5 was identified as a novel oncogene promoting HCC progression via the p53 pathway, suggesting its potential as a therapeutic target.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 10","pages":"3077-3100"},"PeriodicalIF":4.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}