Journal of Cancer最新文献

{"title":"Development of nasopharyngeal carcinoma target delineation: from two-dimensional radiotherapy to adaptive precision radiotherapy.","authors":"Xiaojing Yang, Lijun Liu, Huicai Zhang, Hanru Ren, Jie Fu","doi":"10.7150/jca.125480","DOIUrl":"10.7150/jca.125480","url":null,"abstract":"<p><p>Nasopharyngeal carcinoma (NPC) is mainly treated with radiotherapy. With the advancements of imaging and radiotherapy techniques, the delineation of NPC target areas has evolved from empirical field setting in the two-dimensional era to three-dimensional conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), and image-guided adaptive radiotherapy (ART), significantly improving treatment accuracy and safety. This review systematically explores the development process of target area delineation in NPC, focusing on the evolution and standardization of target areas in the nasopharynx and neck lymph nodes, and combines the role of multimodal imaging such as MRI and PET-CT in target area delineation. The article further examines the clinical response strategies and research trends of target area changes after induction chemotherapy (IC), and looks forward to the potential of ART and artificial intelligence in future target area delineation. The review aims to provide clinical practitioners with a scientific, rational, and personalized approach to target delineation, optimizing treatment plans and improving clinical outcomes.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 6","pages":"1179-1186"},"PeriodicalIF":3.4,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dehydroleucodine Induces ROS-Mediated Mitochondrial Apoptosis and G2/M Cell Cycle Arrest in Oral Squamous Cell Carcinoma.","authors":"Johnathon Lee, Tsung-Ming Chang, Chia-Jung Lee, Ju-Fang Liu, Hsin-Hua Chou","doi":"10.7150/jca.127924","DOIUrl":"10.7150/jca.127924","url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor clinical outcomes due largely to recurrence and therapy resistance. Dehydroleucodine (DhL) is a sesquiterpene lactone derived from <i>Asteraceae</i> species, which has demonstrated anticancer activity in several tumor models. However, its therapeutic relevance in OSCC has not been established. This study investigated the antitumor effects of DhL and the mechanisms underlying its activity in OSCC using complementary <i>in vitro</i> and <i>in vivo</i> approaches. DhL significantly suppressed cell viability and clonogenic growth in HSC3 and SCC4 cells, with relatively low cytotoxicity toward normal gingival fibroblasts (HGF-1) under the tested conditions. The underlying mechanisms involved apoptotic cell death and G2/M phase arrest, accompanied by reduced cyclin B1 and CDK1 expression. DhL was also shown to promote mitochondrial dysfunction, as indicated by loss of mitochondrial membrane potential, increased Bax/Bcl-2 ratio, elevated cleaved caspase-3 expression and activity, and increased intracellular reactive oxygen species (ROS) generation. Pretreatment with the antioxidant N-acetylcysteine partially attenuated apoptosis and cell cycle arrest, suggesting that ROS plays a role in both responses. Systemic DhL treatment in an <i>in vivo</i> xenograft model significantly inhibited tumor growth and increased cleaved caspase-3 expression in tumor tissue without a significant loss of body weight. Together, these findings identify DhL as a potent suppressor of OSCC growth, which acts through ROS-associated mitochondrial apoptosis and G2/M arrest, supporting further preclinical evaluation of DhL as a candidate therapeutic agent for OSCC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 6","pages":"1165-1178"},"PeriodicalIF":3.4,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of an m6A-Derived Prognostic Signature in Lung Adenocarcinoma.","authors":"Zheng Shao, YongLi Situ, Bairu Lai, Ying Xu, Jv Chen, Li Deng, QinYing Xu, Meng Liang, Zhu Liang, ZhanQiang Xie","doi":"10.7150/jca.134792","DOIUrl":"10.7150/jca.134792","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) exhibits extensive molecular heterogeneity and poor prognosis, necessitating novel epigenetic biomarkers. N6-methyladenosine (m6A) modification, a pivotal epigenetic regulator of RNA, is frequently dysregulated in LUAD, yet its systematic roles in clinical prognosis and the tumor microenvironment (TME) remain poorly elucidated.</p><p><strong>Methods: </strong>Transcriptomic profiles and clinical data from large-scale cohorts were integrated and analyzed. Unsupervised consensus clustering based on 47 m6A-related genes (MRGs) was performed to distinguish distinct molecular subtypes. A prognostic model was developed via LASSO-Cox regression algorithm and further validated in multiple independent cohorts. Immune infiltration, tumor mutational burden (TMB), immunotherapy response (TIDE/IPS), and chemotherapy sensitivity were analyzed, complemented by single-cell RNA sequencing.</p><p><strong>Results: </strong>Two distinct m6A-related gene clusters (mRGclusters A and B) were identified. Patients in cluster B exhibited inferior survival outcomes, higher m6A pathway activity, and significant enrichment of cell cycle-related pathways. The eight-gene signature successfully stratified patients into high-risk (HR) and low-risk (LR) subgroups. Patients in the HR group presented significantly worse overall survival (P < 0.05), higher TMB levels, and upregulated expression of multiple immune checkpoint genes such as <i>LAG3</i> and <i>PDCD1</i>. <i>CSMD3</i> mutations were capable of improving the survival of HR patients by facilitating the infiltration of natural killer cells and follicular helper T cells. The signature independently predicted prognosis (AUC: 0.70-0.84) and treatment response: LR patients favored immunotherapy (lower TIDE, higher IPS), while HR patients were sensitive to chemotherapy (e.g., Bosutinib, Tozasertib).</p><p><strong>Conclusion: </strong>This transcriptome-derived m6A-associated prognostic model can effectively predict clinical survival outcomes and therapeutic response in LUAD patients. Combined with immune landscape, genomic mutation profiles and single-cell transcriptomic evidence, this signature provides a reliable basis for personalized risk stratification and rational treatment choice.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 6","pages":"1134-1154"},"PeriodicalIF":3.4,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiological Trends and Shared Molecular Signatures of Pancreatic Ductal Adenocarcinoma and Diabetes: An Integrative Analysis Based on Global Burden of Disease and Gene Expression Omnibus Datasets.","authors":"Jiaxi Zhang, Zhibin Liu, Ke Huang, Junkoo Yi, Myoung Ok Kim","doi":"10.7150/jca.134528","DOIUrl":"10.7150/jca.134528","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide, and diabetes mellitus has been recognized as both a risk factor for and a potential consequence of PDAC. However, the epidemiological trends and shared molecular mechanisms underlying this association are not completely understood.</p><p><strong>Methods: </strong>We conducted an integrative analysis combining population-level epidemiological data and transcriptomic datasets. Global trends in PDAC incidence, PDAC-related mortality, and diabetes incidence from 2013 to 2023 were obtained from the Global Burden of Disease (GBD) database. A meta-analysis was performed to quantify the association between diabetes and PDAC risk. In addition, gene expression datasets focusing on PDAC (GSE15471) and type 2 diabetes mellitus (T2DM; GSE20966) were obtained from the Gene Expression Omnibus database, differentially expressed genes were identified, and upregulated genes associated with both PDAC and T2DM were examined using heatmaps.</p><p><strong>Results: </strong>Continuous increases in global PDAC incidence, mortality due to PDAC, and the incidence of diabetes were identified in the GBD data. The meta-analysis of eight studies demonstrated that diabetes was significantly associated with an increased risk of PDAC (pooled relative risk = 1.94, 95% CI: 1.78-2.11). Transcriptomic analyses identified five genes-<i>FXYD3</i>, <i>LAMC1</i>, <i>MDFIC</i>, <i>SOCS3</i>, and <i>TREM2</i>-that were consistently upregulated in both PDAC and T2DM-affected tissues.</p><p><strong>Conclusion: </strong>This integrative epidemiological and transcriptomic analysis demonstrates that diabetes and PDAC share not only similar global disease trends but also a significant epidemiological association and common molecular alterations. The identified shared genes may represent molecular links between diabetes and PDAC, providing new insights applicable to risk stratification and mechanistic studies.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 6","pages":"1125-1133"},"PeriodicalIF":3.4,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CellVizio^® System for Mesothorax Lymphadenopathy Rapid on Site, 18G needle: Pros and Cons.","authors":"Paul Zarogoulidis, Wolfgang Hofenforst-Schwidt, Haidong Huang, Stavros Tryfon, Yifei Zhang, Guoren Ma, Kyriakos Amarantidis, Elena Maragouli, Vasilis Papadopoulos, Eleni-Isidora Perdikouri, Vagelis Voulgaris, Lutz Freitag, Chrysoula Margioula-Siarkou, Theodora Tsiouda, Paschalis Ntolios, Stamatis Petousis, Konstantina Triantafylopoulou, Kosmas Tsakiridis, Nikolaos Courcoutsakis, Sofia Baka, Dimitris Baloukas, Paschalis Steiropoulos, Bojan Zaric, Xiaping Shen","doi":"10.7150/jca.136122","DOIUrl":"10.7150/jca.136122","url":null,"abstract":"<p><strong>Introduction: </strong>The best tissue sample is still very important for the diagnosis of mesothorax lymphadenopathy. In the past 20 years endobronchial ultrasound (EBUS) has been used efficiently in most cases of primary lung cancer disease or metastatic disease. Several new type of needles have been created such 19G, 18G and hybrid biopsies with cryoprobes. Rapid on-site evaluation (ROSE) is used as an additional initial diagnostic tool. Confocal microscopy is a method of rapid on-site evaluation.</p><p><strong>Patients and methods: </strong>One hundred patients with mesothorax lymphadenopathy were biopsied with ebus and two groups were created one with rapid on-site evaluation with confocal microscopy and one by an operator with microscopic evaluation with sample preparation on cytoglasses. Our main objective was to assess parameters such as time, false negative results between the two techniques and technical issues such as the accessibility and evaluation between the two techniques. Safety was also evaluated.</p><p><strong>Results: </strong>Rapid on-site evaluation is more cost efficient with a cytologist on site, however; with a higher rate of false negative results. Accessibility with the Cellvizio^® catheter was less possible in a few cases due to rigid angles within the airways especially for small lymphnodes ≤ 1.5 cm (L4L mainly).</p><p><strong>Discussion: </strong>Confocal is a safe and time-efficient technique for mesothorax lymphadenopathy. A high level of training is required for pulmonary physicians in order to assess the novel imaging technique. Definitely different parts of the lymphnode have to reached and evaluated in order to have a proper initial evaluation.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 6","pages":"1187-1194"},"PeriodicalIF":3.4,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-150-5p at the Interface of Cancer Biology and Immune Regulation: Dual Roles, Mechanisms, and Therapeutic Opportunities.","authors":"Iris Lin, Pardis Shirkani, Cathie Garnis","doi":"10.7150/jca.119966","DOIUrl":"10.7150/jca.119966","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally and play crucial roles in cancer biology and immune function. Among them, miR-150-5p has emerged as a key regulator with complex, context-dependent roles in both tumorigenesis and immune cell differentiation. This review provides a comprehensive synthesis of current knowledge on miR-150-5p, highlighting its dual function as a tumor suppressor or oncogene depending on cancer type and cellular context. We examine its involvement in hematologic malignancies and solid tumors, detailing the molecular mechanisms through which it influences proliferation, apoptosis, and metastasis. Particular emphasis is placed on the role of extracellular vesicle (EV)-associated miR-150-5p as a modulator of the tumor microenvironment (TME), including its impact on angiogenesis, immune evasion, and intercellular communication. We further explore miR-150-5p's regulation of key immune cell subsets-such as macrophages, dendritic cells, T cells, and natural killer cells-and its implications for anti-tumor immunity. Finally, we discuss the therapeutic potential and challenges of targeting miR-150-5p, including delivery barriers, off-target effects, and opportunities for personalized medicine. By integrating recent findings, this review underscores miR-150-5p's value as both a biomarker and a therapeutic target in cancer immunology.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 6","pages":"1105-1116"},"PeriodicalIF":3.4,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148295143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MRI-Based Habitat Radiomics for Differentiating Early-Stage Endometrial Carcinoma from Submucous Leiomyoma: A Multicenter Validation Study.","authors":"Hao Tian, Anqi Yan, Lei Cao, Ziyi Pan, Yuyan Guo, Bo Shen, Jing Wang, Jingxuan Jiang","doi":"10.7150/jca.129931","DOIUrl":"10.7150/jca.129931","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the utility of magnetic resonance imaging (MRI)-based habitat radiomics for preoperatively distinguishing early-stage endometrial carcinoma (EC) from submucous leiomyoma (SML).</p><p><strong>Materials and methods: </strong>A retrospective study was conducted on uterine lesions patients who underwent MRI from three hospitals. The k-means clustering algorithm was applied to segment the MRI into distinct habitats based on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and apparent diffusion coefficient (ADC) maps. Radiomic features were extracted from whole-tumor and these habitats and selected by the Pearson correlation coefficient and least absolute shrinkage and selection operator (LASSO) regression. A logistic regression (LR) model was constructed by these radiomics in the training set.</p><p><strong>Results: </strong>A total of 231 eligible patients were incorporated, 97 EC and 134 SML confirmed by histopathology. In the training cohort, the AUCs of the models based on features from the whole-tumor, habitat_1, habitat_2, and habitat_3 were 0.826, 0.787, 0.770, and 0.907, respectively, while in the test and external validation cohorts, the corresponding AUCs were 0.774/0.751, 0.486/0.608, 0.663/0.514, and 0.858/0.881. Compared with whole-tumor model, habitat_3 model demonstrated incrementally improved predictive performance in the external validation cohort (0.881 [95% CI: 0.799-0.934]).</p><p><strong>Conclusion: </strong>MRI-based habitat radiomics offers incremental improvement for preoperative differentiation between early-stage EC and SML.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"1073-1081"},"PeriodicalIF":3.4,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vemurafenib Induces Apoptosis via JNK Activation and AKT Inhibition in Hepatocellular Carcinoma.","authors":"Yu Rim Cho, Ke Huang, Zhibin Liu, Hyeonjin Kim, Chae Yeon Kim, Lei Ma, Nangwon Yee, Chae Rim Kim, Geun Hye Park, Jiaxi Zhang, Zae Young Ryoo, Sung Hyun Kim, Myoung Ok Kim","doi":"10.7150/jca.130097","DOIUrl":"10.7150/jca.130097","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and remains one of the leading contributors to cancer-related mortality worldwide, primarily due to the disease's therapeutic resistance and marked tumor heterogeneity. Among the molecular mechanisms implicated in HCC progression, the dysregulation of the JNK and PI3K/AKT signaling pathways plays a critical role in tumor initiation, cell proliferation, and cell survival. Vemurafenib, a clinically approved inhibitor of mutant BRAF kinase, has shown robust antitumor activity across multiple malignancies. However, its therapeutic utility in HCC remains largely unexplored.</p><p><strong>Methods: </strong>We investigated the anticancer effects of vemurafenib in two human HCC cell lines.</p><p><strong>Results: </strong>Vemurafenib treatments led to significant declines in cell viability and colony formation, accompanied by marked reductions in the migratory and invasive behaviors of HCC cells. Mechanistically, vemurafenib enhanced JNK pathway activation while suppressing AKT phosphorylation.</p><p><strong>Conclusion: </strong>Vemurafenib markedly inhibited HCC cell proliferation and metastasis, which was accompanied by a pronounced induction of apoptosis and G0/G1 phase cell-cycle arrest. At the signaling level, these cellular responses were linked to enhanced JNK activation and the suppression of AKT phosphorylation, suggesting that vemurafenib may serve as a potential therapeutic agent for HCC.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"1094-1104"},"PeriodicalIF":3.4,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13190229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Thyroid Biomarkers for Diagnosing Malignant Thyroid Nodules: A Machine Learning Approach with External and Causal Validation.","authors":"Qingling Gu, Faling Xue, Xiaojing Shi, Zhuoling Zheng, Wenqing Wang, Zhuolin Yang, Yiyu Zhang, Wenqi Huang, Min Huang, Zhongxing Wang, Jiali Li","doi":"10.7150/jca.131422","DOIUrl":"10.7150/jca.131422","url":null,"abstract":"<p><strong>Background: </strong>Thyroid nodules (TNs) are common, and accurate malignancy risk stratification is critical for clinical decision-making. Although serum thyroid biomarkers are routinely measured, their contribution to malignancy discrimination remains insufficiently characterized. Thus, we aimed to develop a practical and biologically grounded model for identifying malignant TNs using routinely clinical data.</p><p><strong>Methods: </strong>We retrospectively analyzed 5537 patients initially diagnosed with TNs from two hospitals, including 66.23% with malignant TNs. Diagnostic models were developed using logistic regression and machine learning approaches with internal and external validation. Causal associations were assessed using Mendelian randomization (MR), and biological relevance was further examined based on TCGA data.</p><p><strong>Results: </strong>Younger age (OR = 0.96 [0.95-0.97], P < 0.001) and lower thyroglobulin (Tg) levels (OR = 0.64 [0.61-0.67], P < 0.001) were identified as key risk factors for malignant TNs. The two-factor model achieved AUCs of 0.755 (training), 0.735 (internal validation), 0.76 (temporal validation), and 0.784 (external validation) among various cohorts, and demonstrated incremental value to TI-RADS. An interactive web-based nomogram was developed as a proof-of-concept tool to support clinical utility. MR analysis supported a positive causal relationship between Tg and benign TNs (β = 0.62, P = 0.006), while TCGA data confirmed the inverse association between Tg and malignant TNs (OR = 0.14, P < 0.001).</p><p><strong>Conclusion: </strong>A simple model integrating age and routine serum Tg demonstrates robust and generalizable performance for malignancy risk stratification of TNs. By integrating clinical prediction with causal inference and biological validation, this study provides a complementary tool to existing ultrasound-based risk stratification systems.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"1082-1093"},"PeriodicalIF":3.4,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13190228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Bulk and Single-Cell Transcriptome Profiling of Telomere-Related Genes Reveals a Robust Prognostic Signature and Immunotherapeutic Landscape in Neuroblastoma.","authors":"Yeerfan Aierken, Lulu Zheng, Tao Liu, Kezhe Tan, Zhibao Lv","doi":"10.7150/jca.129718","DOIUrl":"10.7150/jca.129718","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Neuroblastoma (NB) is the most common extracranial solid tumor in children with poor overall survival. Increasing evidence indicates that telomeres contribute to tumorigenesis and influence cancer prognosis. However, the biological and clinical implications of telomere-related genes (TRGs) in NB remain poorly defined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;We integrated data from multiple independent cohorts to elucidate the roles of TRGs in NB. Differential expression and weighted gene co-expression network analyses (WGCNA) were performed to identify telomere-related differentially expressed genes (TRDEGs) linked to patient survival. Consensus clustering based on TRDEG expression patterns was conducted to stratify molecular subtypes, followed by functional enrichment analysis. A prognostic signature was then built using machine-learning algorithms to predict clinical outcomes and potential therapeutic responses. Single-cell RNA sequencing (scRNA-seq) data were used for signature gene expression validation and to guide functional candidate selection. Quantitative RT-PCR was performed to verify the TRDEG signature, and functional assays were performed to explore the role of &lt;i&gt;PSAT1&lt;/i&gt; in NB progression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;First, we identified 103 telomere-related differentially expressed genes (TRDEGs) significantly linked to NB patient survival. Consensus clustering of TRDEGs revealed two NB molecular subtypes with distinct biological processes and clinical outcomes. We established an eight-gene prognostic signature (&lt;i&gt;ARHGAP23, CHD5, E2F3, ELOVL6, FEN1, GMPS, LRR1,&lt;/i&gt; and &lt;i&gt;PSAT1&lt;/i&gt;) that demonstrated high predictive accuracy, with 1-, 3-, and 5-year survival AUCs of 0.885, 0.903, and 0.911, respectively. The model showed consistent robustness across validation cohorts. Multivariate Cox regression confirmed the risk score as an independent prognostic factor. Integrating the risk score with clinical parameters within a nomogram yielded superior prognostic performance compared with traditional stratification schemes. High-risk patients showed decreased immune cell infiltration and increased immune evasion patterns, corresponding to poorer immunotherapy response. Distinct chemosensitivity profiles characterized the two risk groups. Quantitative RT-PCR validated the TRDEG signature. Last, &lt;i&gt;PSAT1&lt;/i&gt; was identified as a representative gene within the TRDEG signature through integration of scRNA-seq data, exhibited tumor-cell-specific expression, and was experimentally confirmed to promote NB cell proliferation, inhibit apoptosis, and enhance migratory capacity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;TRGs play a pivotal role in shaping NB prognosis and treatment response. The validated TRDEG signature provides a foundation for individual risk assessment and future development of precision therapies and immunotherapeutic strategies. Among these genes, &lt;i&gt;PSAT1&lt;/i&gt; emerges as a key oncogenic driver.&lt;/","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 5","pages":"1050-1072"},"PeriodicalIF":3.4,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148015677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}