Journal of Cancer最新文献

{"title":"Comprehensive Characterization and Prognostic Modeling of Efferocytosis-Related Genes in Cutaneous Melanoma.","authors":"Yuliang Sun, Zhihu Ma, Yanlin Li, Anhao Shi, Gang Wang","doi":"10.7150/jca.130446","DOIUrl":"10.7150/jca.130446","url":null,"abstract":"<p><strong>Background: </strong>Cutaneous melanoma (CM) is a highly aggressive skin cancer with poor prognosis in advanced stages. Efferocytosis, the process by which apoptotic cells are cleared by phagocytes, plays a dual role in tumor immunity and progression. However, the comprehensive role of efferocytosis-related genes (EFRGs) in CM remains unclear.</p><p><strong>Methods: </strong>We conducted a multi-omics analysis by integrating transcriptomic data from TCGA, GEO and GTEx databases, identifying differentially expressed genes and performing WGCNA to define EFRG signatures. Based on the expression profiles of differentially expressed EFRGs, we identified molecular subtypes, evaluated immune infiltration using ESTIMATE and ssGSEA. A prognostic EFRG risk scoring model was further constructed and validated using multiple machine learning algorithms. Western blot, CCK8 assay, colony formation assay and Transwell assays were performed to validate the functional role of the screened EFRG.</p><p><strong>Results: </strong>21 DE-EFRGs with significant prognostic value were identified and three distinct molecular subtypes were subsequently defined. The EFRG-based scoring model effectively stratified patients into high- and low-risk groups with distinct survival outcomes and immune microenvironment characteristics. The low-risk group exhibited a more immune-activated phenotype and greater sensitivity to immunotherapy and chemotherapeutic agents. <i>In vitro</i> functional validation revealed that knockdown of one screened EFRG, TTYH3, significantly inhibited melanoma cell proliferation and migration.</p><p><strong>Conclusions: </strong>Our study comprehensively characterizes EFRG patterns in CM and proposes a robust EFRG-based prognostic model. <i>TTYH3</i> is identified as a potential oncogenic effector and therapeutic target. These findings may guide personalized immunotherapy and improve prognostic assessment in melanoma.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1419-1434"},"PeriodicalIF":3.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706488","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":"GPCRs interaction with LGR5: Implications to cancer stemness.","authors":"Jeetendra K Nag, Ganesh Subedi, Tatyana Rudina, Rachel Bar-Shavit","doi":"10.7150/jca.134767","DOIUrl":"10.7150/jca.134767","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The central role of G-protein coupled receptors (GPCRs) in tumor biology is becoming acknowledged. Yet their involvement in cancer stem cells (CSCs) niche is unknown. Molecular mechanisms of CSCs allow self-formation capacity, resistance to chemotherapy and immune therapy.</p><p><strong>Methods: </strong>Western blots, Co-immunoprecipitation (co-IP) analysis, RT-PCR, <i>Lef/Tcf</i> luciferase activity and Alpha Fold3 HANDDOCK v2.4 protein-protein docking interactions.</p><p><strong>Results: </strong>It is demonstrated that protease-activated receptor 4 (PAR₄) induces β-catenin levels, co-associates with LRP6 coreceptor and promotes DVL nuclear translocation. PAR₄ induced β-catenin transcriptional activity is shown by TOP<i>flash</i> luciferase assay and enhanced downstream target genes levels. Significantly, PAR₄ co-binds leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) as determined by co-IP and protein-protein docking analyses. We show also that another GPCR namely, GPR25 specifically expressed in the gastrointestinal tract cells, elicits β-catenin stabilization and co associates with LGR5.</p><p><strong>Conclusions: </strong>As was previously shown for PAR₂ also PAR₄ and GPR25 elicit β-catenin stabilization and they co-link with LGR5. We propose that GPCRs that potently induce β-catenin stabilization are potentially involved in the regulation of CSCs niche. Our data may provide future directions for potential partners in the cancer stem cell niche.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 8","pages":"1408-1418"},"PeriodicalIF":3.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706512","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":"Arteannuin B Induces Ferroptosis in Colorectal Cancer Cells via GDF15/HMGCS1/GPX4 Axis.","authors":"Xiaozheng Ou, Jinghong Xu, Yuting Jin, Yanqing Wang, Rongmin Yu, Jianhua Zhu, Weijuan Huang, Liyan Song","doi":"10.7150/jca.128611","DOIUrl":"10.7150/jca.128611","url":null,"abstract":"<p><strong>Purpose: </strong>Drug resistance in colorectal cancer (CRC) necessitates novel therapeutic strategies. This study investigated whether arteannuin B, a sesquiterpene lactone from <i>Artemisia annua</i>, induces ferroptosis in CRC cells and elucidated the underlying molecular mechanism.</p><p><strong>Methods: </strong>Anti-CRC effects were assessed <i>via</i> MTT assays and xenograft models. Proteomics identified differentially expressed proteins. Arteannuin B-induced ferroptosis was confirmed by measuring reactive oxygen species (ROS), lipid peroxidation, Fe²⁺ content, glutathione peroxidase 4 (GPX4) expression, and mitochondrial morphology. Mevalonate pathway regulation was evaluated by western blotting, dual-luciferase assay, and quantification of squalene, coenzyme Q10 (CoQ10), and cholesterol. The role of growth differentiation factor 15 (GDF15) was validated using shRNA knockdown and overexpression DLD-1 cells <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Results: </strong>Arteannuin B showed significant anti-colorectal cancer activity both <i>in vitro</i> and <i>in vivo</i>. The proteomic analysis demonstrated that arteannuin B affected the mevalonate pathway and ferroptosis in DLD-1 cells, and strongly upregulated the expression of GDF15. Arteannuin B increased ROS, lipid peroxidation, malondialdehyde, and iron while decreasing GPX4 expression and causing mitochondrial shrinkage. Arteannuin B inhibited mevalonate pathway enzymes, particularly 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1), reducing squalene, CoQ10, and cholesterol. The knockdown of GDF15 weakened the inhibitory effect of arteannuin B on the mevalonate pathway and GPX4, and reduced the sensitivity of CRC cells to arteannuin B both <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Conclusion: </strong>Arteannuin B triggers ferroptosis-like cell death in CRC cells and suppresses xenograft growth, in association with inhibition of the mevalonate pathway. GDF15 contributes to arteannuin B-mediated suppression of HMGCS1 and GPX4 and to ferroptosis sensitivity.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 7","pages":"1393-1407"},"PeriodicalIF":3.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620131","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":"tsRNA's Biological Function and its Potential Application in Disease Diagnosis and Prognosis.","authors":"Congcong Tang, Qi Tang, Siyuan Tang, Faqing Tang","doi":"10.7150/jca.135857","DOIUrl":"10.7150/jca.135857","url":null,"abstract":"<p><p>Under physiological conditions, tsRNAs regulate mRNA transcription, reverse transcription, and protein translation to mediate cell apoptosis, cell cycle, and epigenetic regulation. Pathogenic tsRNAs are disease-specific or disease-related tsRNAs that are highly express in various diseases and may serve as diagnostic or potential diagnostic biomarkers. Specifically expressed tsRNAs in tumors were screened and obtained from the tumors. Although the mechanisms by which these oncogenic tsRNAs contribute to tumor development remain unclear, they have been shown to be applicable to tumor diagnosis and therapeutic prognosis. This article briefly summarizes pathogenic tsRNAs involved in various diseases and their biological functions. Oncogenic tsRNAs in tumors and their clinical applications have been elaborated upon. The molecular mechanisms of pathological tsRNAs in both general diseases and tumors need to be further investigated in future.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 7","pages":"1384-1392"},"PeriodicalIF":3.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620164","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 transcriptomic analysis identify an ac4C-related signature in lung adenocarcinoma.","authors":"Shuo Wang, Changqing Yang, Xingkai Wang, Zhigang Zhu, Yuxin Xie, Rui Wang, Dan Liu, Jing Feng","doi":"10.7150/jca.135531","DOIUrl":"10.7150/jca.135531","url":null,"abstract":"<p><strong>Background: </strong>N4-acetylcytidine (ac4C) RNA modification is a critical epitranscriptomic regulator of cancer progression, yet its specific biological functions and regulatory patterns in lung adenocarcinoma (LUAD) remain poorly understood. This study aims to characterize the clinical relevance and potential regulatory patterns of ac4C-related features in the LUAD tumor microenvironment (TME).</p><p><strong>Methods: </strong>We integrated bulk RNA-seq data from TCGA and single-cell RNA-seq (scRNA-seq) data from GEO. Weighted gene co-expression network analysis (WGCNA) identified prognosis-related modules. A robust six-gene ac4C-related signature was derived using three consensus machine learning algorithms: LASSO, Random Forest, and SVM-RFE. The signature was further validated using pseudotime trajectory inference, CellChat-based intercellular communication analysis, and <i>in vitro</i> functional assays.</p><p><strong>Results: </strong>The six-gene signature effectively stratified LUAD patients, identifying a high-risk subgroup characterized by poor survival and frequent TP53 mutations. Single-cell analysis suggested that high ac4C-related signature scores were associated with advanced malignant states and enhanced predicted pro-tumorigenic signaling within the TME, particularly involving the EGF, TGFB, and MIF pathways. Pharmacogenomic modeling identified increased sensitivity to CDK and PLK1 inhibitors in high-risk patients. Experimentally, PLK1 silencing significantly suppressed LUAD cell proliferation and migration.</p><p><strong>Conclusions: </strong>This study identifies a potential ac4C-related prognostic signature associated with malignant cell states and predicted communication patterns within the TME, and suggests PLK1 as a candidate therapeutic target in LUAD.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 7","pages":"1331-1345"},"PeriodicalIF":3.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620166","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":"Single-cell Transcriptomics Uncovers the Tumor Microenvironment and Collagen-CD44 Axis in HIV Positive Cervical Squamous Cell Carcinoma.","authors":"Yuxi Ma, Lijun Zhang, Liangfei Niu, Bo Yan, Min Liu","doi":"10.7150/jca.134138","DOIUrl":"10.7150/jca.134138","url":null,"abstract":"<p><strong>Introduction: </strong>Human immunodeficiency virus (HIV) infection markedly increases the incidence and worsens clinical outcomes of cervical squamous cell carcinoma (CSCC). The single-cell landscape of the tumor microenvironment (TME) in HIV positive CSCC (HIV-CSCC) remains poorly defined, and its cellular and molecular differences from HIV negative CSCC are largely unclear.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (scRNA-seq) on tumor tissues from three HIV-CSCC patients without preoperative chemoradiotherapy. Public scRNA-seq data of three HIV negative CSCC cases were integrated as controls. We systematically analyzed cellular composition, transcriptional profiles, metabolic characteristics and intercellular communication networks across groups.</p><p><strong>Results: </strong>Epithelial cells in HIV-CSCC exhibited aggravated malignant phenotypes and metabolic disorders. The C5 epithelial subcluster was strongly associated with poor patient survival. Tumor-infiltrating T cells displayed impaired cytotoxic function. Macrophages predominantly polarized into immunosuppressive M2-like phenotypes with attenuated phagocytosis and antigen presentation. Cancer-associated fibroblasts (CAFs) acted as the core regulatory hub in HIV-CSCC TME and mediated cell crosstalk mainly via the collagen-CD44 signaling axis. Upregulated CD44 was an independent prognostic factor for unfavorable survival in HIV positive patients.</p><p><strong>Conclusions: </strong>HIV-CSCC is characterized by a highly immunosuppressive TME and extensive stromal remodeling driven by activated CAFs. The collagen-CD44 pathway plays a key role in tumor progression. Our findings reveal the molecular mechanism of HIV-CSCC and identify CD44 as a promising therapeutic target for this disease.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 7","pages":"1346-1361"},"PeriodicalIF":3.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620169","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":"Long-Term Empagliflozin Treatment (50 Days) Attenuates Protease Activity, Migration, and Stemness-Associated Phenotypes in BFTC-909 Renal Pelvis Transitional Cell Carcinoma Cells.","authors":"Yi-Hsun Lee, Pei-Ni Chen, Yi-Hsien Hsieh, Yi-Cheng Chu, Li-Jeng Chen, Chin-Yin Lin, Shun-Fa Yang, Horng-Rong Chang","doi":"10.7150/jca.132959","DOIUrl":"10.7150/jca.132959","url":null,"abstract":"<p><p>Empagliflozin is a sodium-glucose cotransporter 2 inhibitor widely prescribed for the treatment of type 2 diabetes mellitus. It promotes urinary glucose excretion by inhibiting renal glucose reabsorption. Although empagliflozin has been widely used in clinical practice, its effects and underlying mechanisms related to metastasis, cytokine secretion, and stemness-associated phenotypes in renal pelvis transitional cell carcinoma (TCC) remain poorly understood. In this study, we investigated the long-term (50 days) effects of empagliflozin (5 μM) on BFTC-909 human renal pelvis TCC cells. Prolonged empagliflozin treatment suppressed the migration of tumor cells and the proteolytic activities of matrix metalloproteinase-2 and urokinase-type plasminogen activator. In addition, empagliflozin markedly reduced the viability and self-renewal capacity of BFTC-909 cells. Analysis of conditioned media revealed that long-term empagliflozin exposure significantly reduced the secretion of interleukin-1Ra, interleukin-8, granulocyte colony-stimulating factor, and vascular endothelial growth factor. Together, these findings suggest that empagliflozin suppresses the protease activity, tumor invasiveness, and stemness-associated phenotypes of renal pelvis TCC cells. Overall, this study indicates that long-term empagliflozin treatment reduces the metastatic potential of BFTC-909 renal pelvis TCC cells and highlights the need for additional <i>in vivo</i> and clinical investigations.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 7","pages":"1373-1383"},"PeriodicalIF":3.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620222","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":"A digital polymerase chain reaction method targeting non-recombined T-cell receptor sequences aids in diagnosing primary cutaneous T-cell lymphomas.","authors":"Chien-Chin Chen, Cheng-Lin Wu, Bo-Jiun Tzeng, Pin-Jun Chen, Wan-Li Chen, Sern Yan Lim, Yi-Ling Chen, Yi-Lin Chen, Chung-Liang Ho, Tsunglin Liu","doi":"10.7150/jca.136694","DOIUrl":"10.7150/jca.136694","url":null,"abstract":"<p><strong>Background: </strong>Diagnosing primary cutaneous T-cell lymphoma (PCTCL) relies on the comprehensive evaluation of clinical presentation, histopathology, immune profile, and molecular testing. Regarding molecular testing, the BIOMED-2 assay is most commonly used for detecting monoclonality of T-cell receptor (TCR) genes. However, its sensitivity is not ideal for PCTCLs, and a supplementary test is required. We recently found that the ratios of non-recombined TCR sequences J2-2P and J2-3 of the <i>TCRβ</i> gene were higher in T-cell lymphoma (TCL) samples than in non-TCL cases. Here, we aim to evaluate the diagnostic value of this novel biomarker for PCTCL via digital polymerase chain reaction (dPCR) as a supplementary method to the BIOMED-2 clonality assay.</p><p><strong>Methods: </strong>Formalin-fixed paraffin-embedded tissue samples of clinicopathologically proven PCTCL cases with a negative BIOMED-2 clonality result were retrospectively retrieved, and the clinicopathological characteristics were collected. After RNA extraction and quality checking, dPCR was performed on PCTCL specimens and control samples to quantify the J2-2P and J2-3 sequences.</p><p><strong>Results: </strong>We collected 35 skin biopsy samples from patients with early-stage PCTCL and 11 inflammatory dermatoses as controls. Ratios of the J2-2P to J2-3 concentration in controls ranged from 0.03 to 0.55% (mean ± standard deviation: 0.21 ± 0.17%). In contrast, 25 of the 35 (71.42%) PCTCL specimens exhibited J2-2P/J2-3 ratios exceeding the defined upper limit of the control group.</p><p><strong>Conclusion: </strong>Our dPCR assay on the non-recombined <i>TCRβ</i> sequences revealed that a majority of the PCTCL cases with a negative BIOMED-2 result had higher ratios of the J2-2P to J2-3 concentration than inflammatory dermatoses. Therefore, this approach may supplement the BIOMED-2 clonality assay for diagnosing PCTCL.</p>","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 7","pages":"1362-1372"},"PeriodicalIF":3.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620125","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":"Cell-Specific DNA Methylation Markers in Plasma cfDNA Reveal Diagnostic Potential for Head and Neck Cancer.","authors":"Tianci Wang, Fei Han, Yuxuan She, Mengju He, Yicen Ding, Qi Mei, Yani Kang","doi":"10.7150/jca.133470","DOIUrl":"10.7150/jca.133470","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;Head and neck cancer ranks as the seventh most common type of cancer worldwide. For patients diagnosed at advanced stages, the five-year survival rate remains below 40%, underscoring the urgent need for early detection strategies. However, current diagnostic approaches face considerable limitations. Furthermore, tissue biopsy remains invasive and impractical for routine screening. In light of these challenges, this study aims to identify and validate plasma cell-free DNA (cfDNA) methylation markers capable of enabling auxiliary assessment and facilitating prognosis assessment in head and neck cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;To achieve this goal, we first analyzed whole-genome bisulfite sequencing (WGBS) data from 205 samples covering 39 healthy tissue types. This comprehensive analysis was conducted to establish a baseline methylation landscape and identify methylation sites specifically associated with head and neck cells. Subsequently, differentially methylated CpG sites were screened by comparing head and neck tissues with other healthy tissues. To enhance the robustness and specificity of potential markers, more than 5 adjacent cell-specific methylated CpG sites located within 150 base pairs of each other were clustered into composite methylation markers, thereby reducing background noise and improving signal detection. These candidate markers then underwent a stringent specificity test to confirm their exclusive enrichment in head and neck tissues. Finally, one of the most promising markers was experimentally validated in plasma cfDNA samples collected from head and neck cancer patients compared with healthy controls, using targeted bisulfite sequencing to assess their detection performance in liquid biopsies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Through comprehensive analysis of WGBS data from healthy tissue samples, a total of 1,157 tissue-specific methylation sites were identified, including 146 hypermethylated and 1,011 hypomethylated sites exclusive to head and neck tissues. By clustering adjacent CpG sites within a 150-base-pair window, these were consolidated into 11 composite methylation markers, each representing a distinct genomic region with coordinated methylation patterns. Subsequent specificity testing confirmed that all composite markers exhibited strong cell-type specificity, with minimal background methylation signals detected across other tissue types. This high specificity underscores their potential for accurate tissue-of-origin inference. Validation experiments in plasma cfDNA samples further demonstrated that methylation fragments corresponding to these composite markers were consistently detectable in cancer patients but entirely absent in healthy individuals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study systematically characterizes cell-specific methylation signatures of head and neck tissues and provides preliminary evidence for the feasibility of utilizing composite cfDNA methylation","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 7","pages":"1318-1330"},"PeriodicalIF":3.4,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620173","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":"A Prognostic Risk Model for Hepatocellular Carcinoma Integrating Ferroptosis and Metabolic Reprogramming Signatures.","authors":"Hao Ling, Yanzhu Hu","doi":"10.7150/jca.135837","DOIUrl":"10.7150/jca.135837","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hepatocellular carcinoma (HCC) continues to impose a heavy global health burden, with high incidence and mortality. The disease is highly heterogeneous and is commonly detected at late stages, which compromises treatment outcomes. Ferroptosis and metabolic reprogramming are increasingly recognized as key processes in HCC development; however, their roles in disease progression and therapeutic response remain incompletely understood. This research aimed to identify genes related to ferroptosis and metabolic reprogramming (FPMRRGs) that may serve as putative biomarkers and therapeutic targets in HCC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The Cancer Genome Atlas (TCGA), including 369 HCC specimens and 50 normal controls, along with two Gene Expression Omnibus (GEO) datasets (GSE10143 and GSE76427), were analyzed using R (v4.3.3). From a curated list of 451 FPMRRGs, differentially expressed genes (DEGs) between tumor and normal tissues were identified. Univariate Cox regression analysis was then conducted to explore their prognostic relevance and to define molecular subtypes of HCC. Specimens were categorized into 2 subtypes using ConsensusClusterPlus, and overall survival differences were evaluated via survival analysis. Functional and pathway enrichment analyses were conducted to investigate the functional roles of these genes. Immune-related features were evaluated using the Mann-Whitney U test. A prognostic risk model was constructed using least absolute shrinkage and selection operator (LASSO) regression followed by multivariate Cox analysis. Model performance was assessed using receiver operating characteristic (ROC) curves and calibration plots. Immune cell infiltration was estimated by single-sample GSEA, and pathway activity differences were examined using gene set variation analysis (GSVA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HCC specimens were divided into 2 molecular subtypes, which demonstrated obvious differences in overall survival and immune-related features, including immune checkpoint gene expression and tumor immune dysfunction and exclusion (TIDE) scores. A prognostic model based on 12 key FPMRRGs demonstrated good predictive performance for 1- and 3-year overall survival, with moderate performance for 5-year survival. The prognostic value and expression patterns of these genes were further validated across independent datasets. In addition, these genes were mainly enriched in pathways linked to fatty acid metabolism and HIF-1 signaling, and were closely associated with patterns of immune cell infiltration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study identified numerous key genes linked to ferroptosis and metabolic reprogramming in HCC and developed a robust prognostic risk model. Our results offer new insight into the molecular basis of HCC and highlight potential biomarkers for more individualized treatment approaches. Further studies, particularly those combining clinical validation with functional expe","PeriodicalId":15183,"journal":{"name":"Journal of Cancer","volume":"17 7","pages":"1295-1317"},"PeriodicalIF":3.4,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13410346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620096","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}