Current gene therapy最新文献

{"title":"Targeting of YKL-40 as a Protumor in Personalized Medicine: A New Dimension in Disease Understanding.","authors":"Hebatallah Ahmed Mohamed Moustafa, Ahmed Umer Sohaib, Iqra Saleem, Asmat Ullah","doi":"10.2174/0115665232332419250213081510","DOIUrl":"10.2174/0115665232332419250213081510","url":null,"abstract":"<p><strong>Background: </strong>Individualization of the therapeutic plan for cancer patients is the essence of modern clinical practice. Standard cancer diagnostic and prognostic factors are invasive, and their value for the stratification of cancer patients with a higher risk of local or distant recurrence is limited. YKL-40 is a protumor glycoprotein linked to the immunosuppressive tumor in a microenvironment and an important biomarker of cell activation, proliferation, and migration.</p><p><strong>Objective: </strong>The objective is to update the review, and molecular and clinical research should investigate novel modalities of targeting this glycoprotein for cancer treatment.</p><p><strong>Methods: </strong>Relevant studies published in the English language were identified by searching PubMed, Google Scholar, and MEDLINE from January 2000 to December 2023. Published studies that specifically elicited the role of YKL-40 as a biomarker in different types of tumors were included.</p><p><strong>Results: </strong>YKL-40 cancer prognostic effect was reported in various cancer types.</p><p><strong>Conclusion: </strong>Since antibodies against YKL-40 can inhibit tumor angiogenesis and cancer progression, it can be suggested as an attractive candidate for chemical cancer therapy and immunomodulation.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"17-26"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Gene Therapy for X-Linked Myotubular Myopathy: Current Progress and Future Challenges.","authors":"Md Sadique Hussain, Gyas Khan, Gaurav Gupta","doi":"10.2174/0115665232388661250430062849","DOIUrl":"10.2174/0115665232388661250430062849","url":null,"abstract":"","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"9-10"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaged Capillary Isoelectric Focusing (icIEF) Platform for Characterization of Charge Variants of Adeno-Associated Virus (AAV) Capsids and Impact on their Transduction Efficiency.","authors":"Brandon Hoyle, Dhimiter Bello, Jonathan Hill, Soumita Das, Jonghan Kim","doi":"10.2174/0115665232369708250327081305","DOIUrl":"10.2174/0115665232369708250327081305","url":null,"abstract":"<p><strong>Objective: </strong>Adeno-Associated Virus (AAV) vectors are comprised of a capsid protein encapsulating a Deoxyribonucleic Acid (DNA) transgene that has been used in the gene therapy field showing potential to treat a range of genetic diseases. Methods in the field of gene therapy should be optimized or enhanced to deepen understanding of AAVs, specifically around charge heterogeneity of capsid species.</p><p><strong>Methods: </strong>In this study, a versatile approach was presented for investigating the charge heterogeneity of AAV capsid proteins of a variety of serotypes. This method employs Imaged Capillary Isoelectric Focusing (icIEF) coupled with native fluorescence imaging detection and has undergone exhaustive validation.</p><p><strong>Results: </strong>Demonstrating its platform nature, this method analyzed seven different AAV serotypes from multiple manufacturing platforms. The distinctive profiles generated for each AAV serotype serve as valuable indicators for both identity confirmation and stability assessment. It was shown that thermal stress and pH conditions play a role in increasing acidic charged variants over time, affecting the charge heterogeneity of AAVs, which can be serotype-specific. Reverse phase LC-MS was used to identify and confirm the increased presence of Post-Translational Modifications (PTMs) that are linked to increasing acidic species variants relative to non-stressed AAVs.</p><p><strong>Conclusion: </strong>These PTMs have biological consequences reflected in the diminished expression of the protein of interest in vitro. This cIEF method successfully analyzed a variety of AAV serotypes, and increasing trends of acidic variants led to reduced <i>in vitro</i> potency.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"1-16"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Extrachromosomal DNA (ecDNA) in Cancer: A New Era of CHK1 Inhibition and Personalized Treatments.","authors":"Komal, Lovekesh Singh, Subrahmanya Sarma Ganti","doi":"10.2174/0115665232390083250526072441","DOIUrl":"10.2174/0115665232390083250526072441","url":null,"abstract":"","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"5-8"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144186746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying ARRB2 as a Prognostic Biomarker and Key Player in the Tumor Microenvironment of Pancreatic Cancer through scPagwas Methodology.","authors":"Gaonan Tian, Chengcheng Liu, Chang Che, Shiqi Ren, Kun Zhang, Pengcheng Zhou, Kaidong Wang, Guanyi Lu, Yuchen Xia, YIfan Wang, Kailai Li, Li Yang, Xiangjun Fan, Lei Wang","doi":"10.2174/0115665232427614250904061700","DOIUrl":"10.2174/0115665232427614250904061700","url":null,"abstract":"<p><strong>Introduction: </strong>Pancreatic Cancer (PC) is recognized as a highly aggressive malignancy and is anticipated to become the second leading cause of cancer-associated deaths across the United States by 2030. Owing to its late-stage diagnosis and the substantial risk of metastasis, current therapeutic strategies exhibit limited efficacy, resulting in a five-year survival rate below 10%. Consequently, identifying reliable biomarkers and therapeutic approaches remains imperative for enhancing treatment effectiveness.</p><p><strong>Methods: </strong>In this study, using the data of Cancer Genome Atlas (TCGA) and Genome-Wide Association Study (GWAS), we identified macrophage subsets and key gene arrb2 closely related to the progression of Pancreatic Adenocarcinoma (PAAD) via the scpagwas method combined with single- cell and bulk transcriptome analysis.</p><p><strong>Results: </strong>The results showed that in macrophage subpopulations closely related to disease progression, the ARRB2 gene was significantly associated with the prognosis of patients, and low expression suggested poor survival outcomes. The high-expression subgroup of ARRB2 exhibited higher sensitivity to a variety of drugs, and i-bet-762 showed strong molecular binding ability with ARRB2. The experimental detection further confirmed the low expression of ARRB2 in PAAD tissue, which provided the basis for its use as a prognostic marker and potential therapeutic target.</p><p><strong>Discussion: </strong>The results of this study suggest that ARRB2 is not only a prognostic biomarker of PAAD but may also be involved in the regulation of metabolic and immune pathways, thereby affecting drug responsiveness. There was a significant difference in drug sensitivity between the high and low-expression subgroups of ARRB2, suggesting that there may be a potential mechanism between the signal pathway and the therapeutic effect, which warrants further functional research. Considering the heterogeneity of the macrophage population and its dual role in tumor promotion and inhibition, in-depth analysis of the context-dependent function of ARRB2 in the immune-rich microenvironment is expected to provide new insights for the development of combination therapy, especially the potential of combining it with BET inhibitors (such as i-bet-762).</p><p><strong>Conclusion: </strong>Macrophages, along with ARRB2, serve an essential function in the progression of PAAD and immune regulation. The identification of ARRB2 as a prognostic biomarker and its involvement in critical oncogenic pathways furnish a theoretical foundation for targeted therapeutic interventions. These discoveries contribute to the ongoing exploration of diagnostic, prognostic, and treatment strategies for PAAD.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"203-222"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the Predominant Role of AEBP1 in Different Types of Cancers with a Focus on Glioblastoma Progression - A Review.","authors":"Rangaraj Kaviyaprabha, Sridhar Muthusami, Thandaserry Vasudevan Miji, Palanisamy Arulselvan, Muruganantham Bharathi","doi":"10.2174/0115665232365878250503091118","DOIUrl":"10.2174/0115665232365878250503091118","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Glioblastoma multiforme (GBM) is a highly deleterious lesion with an increased recurrence rate even after radiotherapy and chemotherapy. In this context, additional biomarkers are needed to curb chemoresistance. Computational approaches help us process the RNA-seq and identify the Differentially Expressed Genes (DEGs) in tumors and adjacent normal regions to identify the diagnostic and therapeutic biomarkers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods and materials: &lt;/strong&gt;In this study, we extensively reviewed the role of AEBP1 in different types of cancer, highlighting its significance as a novel target to prevent collagen deposition. Specifically, the underlying mechanisms of AEBP1 in Glioblastoma were analyzed extensively using computational approaches that include Gene Expression Omnibus (GEO), GEPIA to obtain the TCGA-GBM dataset, and Glioma-BioDP to identify the survival rate in the context of AEBP1 expression associated with patients' age. Meanwhile, Tumor Immune Single-cell Hub 2 was implemented to identify the expression of AEBP1 in immunologically lineaged, cancerous, and stromal cells. In addition to that, the miRNA regulation associated with the AEBP1 expression was predicted by implementing NetworkAnalyst, TarBase v8.0, and CancerMIRNome. We identified the DEGs by examining the GSE121723, GSE184643, and GSE14824 datasets with P-values ≤ 0.05 as statistically significant. Furthermore, we predicted and analyzed the highly expressed genes and identified the survival rate, which significantly stated that the overexpression of AEBP1 was associated with decreased survival rates in GBM patients. The Protein-Protein Interaction network was constructed to identify the correlated gene expression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results and discussion: &lt;/strong&gt;We identified 3695, 37001, and 8855 significantly differentially expressed genes (DEGs). The DEGs were filtered by applying a log2 fold-change cut-off of ≥2.0. Finally, 139 common genes were mapped with the identified DEGs (1338 genes) and SDEGs (500 genes) estimated from the TCGA-GBM dataset. The analysis revealed that 155 genes are commonly upregulated, and survival analyses were performed that described the AEBP1 significantly reduced the GBM patients' survival rate among other genes. The constructed PPI network and correlated expression analysis associated with the AEBP1 expression revealed that COL6A2 and THBS2 might play a significant role in the GBM stage advancements by depositing collagens in the matrix environment. Also, the miRNA analysis revealed that the hsa-miR-128-3p and hsa-miR-512-3p could be targeted as a miRNA marker gene to prevent the GBM progression associated with the AEBP1 expression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;AEBP1 is a multi-cancer drug target, underscoring its diagnostic and prognostic value in different types of cancer preventive medicine. It influences tumor growth, metastasis, and immune evasion in cancers like adrenocortical, oral, breast, bladder, g","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"1-28"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Paradigm Shift in Hemophilia Care: The Promise of Gene Therapy.","authors":"Safia Fathima Anver Pasha, Tasnim Fathima Khalifa Anver, Suresh Kumar Srinivasamurthy","doi":"10.2174/0115665232389378250727013548","DOIUrl":"10.2174/0115665232389378250727013548","url":null,"abstract":"<p><strong>Introduction: </strong>The discovery of the gene as the primary unit of inheritance marked the beginning of intensive research into targeted genome modifications for treating rare genetic diseases. Despite conventional approaches such as continuous factor replacement or novel non-factor therapies, the need for a one-time infusion and long-term sustenance of clotting factors is evident. This review focuses on gene therapies discovered to treat patients with hemophilia. This narrative review seeks to highlight the current potential of gene therapies for hemophilia, elucidate their mode of action, and assess their long-term effectiveness and clinical significance.</p><p><strong>Methods: </strong>A literature search in PubMed, Embase, Google Scholar, and Scopus databases was done using search terms like gene therapy, viral vectors, Roctavian, hemophilia, etranacogene dezaparvovec, AAV, and FIX-Padua variant.</p><p><strong>Results: </strong>Following intensive clinical trials and successful outcomes, the currently available FDAapproved gene therapies include valoctocogene roxaparvovec (Roctavian) for hemophilia A and etranacogene dezaparvovec (Hemgenix), and fidanacogene elaparvovec (Beqvez) for hemophilia B, and an antibody-based therapy, Marstacimab (Hympavzi) for both hemophilia A and B.</p><p><strong>Discussion: </strong>Decades of clinical research on introducing gene therapy as a potential therapy for hemophilia A and B have paved the way for successful discovery to overcome the long-term burden of factor replacement and other adjunct therapies. Gene therapy has shown persistent success in hemophilia, with clinical trials demonstrating long-term expression of functional clotting factors (Factor VIII or IX). This has reduced bleeding episodes remarkably and the need for regular factor replacement therapy. Yet the drugs need to be studied further to assess long term safety and efficacy following administration.</p><p><strong>Conclusions: </strong>Gene therapy has shown new possibilities in hemophilia, with many patients achieving near-normal levels of clotting factors and experiencing a significant reduction in bleeding episodes. However, challenges remain, including potential declines in Factor VIII levels over time, immune responses to viral vectors, and high treatment costs. Ongoing research is focused on improving durability, expanding eligibility, and exploring alternative delivery methods.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"1-17"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Novel Biomarkers of Bacterial Lipopolysaccharides in Diabetic Nephropathy via Transcriptomics and Mendelian Randomization.","authors":"Yaxian Ning, Jianqin Wang, Xiaochun Zhou, Gouqin Wang, Lili Zhang","doi":"10.2174/0115665232353811250527053550","DOIUrl":"10.2174/0115665232353811250527053550","url":null,"abstract":"<p><strong>Background: </strong>Dysbiosis of Intestinal Flora Lipopolysaccharides (LPS) is implicated in Diabetic Nephropathy (DN), yet the underlying mechanisms remain unclear. This study aims to elucidate the causal relationship between bacterial LPS and DN, with the goal of informing targeted therapeutic strategies.</p><p><strong>Methods: </strong>DN datasets GSE30528 and GSE96804 were analyzed. Bacterial LPS-related genes (LPS-RGs) were retrieved from the Gene Set Enrichment Analysis (GSEA) database. Differential expression analysis identified differentially expressed genes (DEGs), which were cross-referenced with LPS-RGs to derive DE-LPS-RGs. Mendelian randomization (MR) was applied to explore correlations between exposure factors and outcomes using GWAS data. miRNA-mRNA and TFmRNA regulatory networks were constructed using data from the TarBase and ENCODE databases, and potential therapeutic agents were identified through the DGIdb database.</p><p><strong>Results: </strong>Seven DE-LPS-RGs were identified, with CD14 and LY86 selected as biomarkers. GSEA and GeneMANIA analyses indicated that these genes participate in signal transduction and chargelike receptor signaling pathways. The regulatory networks demonstrated that LY86 interacts with miRNA hsa-mir-26a-5p, while TF ELK1 regulates both CD14 and LY86. Additionally, CD14 was associated with three potential drugs: VB-201, IC14, and Lovastatin.</p><p><strong>Conclusion: </strong>CD14 and LY86 represent promising biomarkers for DN, offering new perspectives for its prediction, diagnosis, and therapeutic intervention.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"1-23"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning-Driven PCDI Classifier for Invasive PitNETs.","authors":"Guanyu Wang, Song Yan, Luyang Zhang, Lu Lin, Rentong Liu, Yiling Han, Yan Zhao","doi":"10.2174/0115665232399193250529074831","DOIUrl":"10.2174/0115665232399193250529074831","url":null,"abstract":"<p><strong>Introduction: </strong>Aggressive Pituitary Neuroendocrine Tumors (PitNETs) pose significant therapeutic challenges due to their invasive behavior and resistance to conventional therapies. Current prognostic markers lack the ability to capture molecular heterogeneity, necessitating novel biomarkers. Dysregulated Programmed Cell Death (PCD) pathways are implicated in tumorigenesis, but their prognostic relevance in invasive PitNETs remains unexplored.</p><p><strong>Methods: </strong>GEO datasets (GSE51618, GSE169498, GSE260487) were analyzed to identify differential gene expression between noninvasive and invasive PitNETs. A curated panel of 1,548 PCDrelated genes was integrated. Machine learning (LASSO regression and SVM-RFE) was employed to construct a PCD-associated Index (PCDI). For validation, ROC analysis, immune infiltration assessment (CIBERSORT, TIMER, ssGSEA), and experimental validation via RT-qPCR were performed.</p><p><strong>Results: </strong>The PCDI, comprising 11 genes (e.g., FGFR3, MAPK11, SLC7A11), distinguished invasive from noninvasive PitNETs with high accuracy. High-PCDI tumors exhibited enriched metabolic pathways and immune activation. Consensus clustering stratified PitNETs into two molecular subtypes (C1/C2), with C2 (high-PCDI) showing elevated immune scores and pathway activity. Experimental validation confirmed the differential expression of key genes in invasive tumors (*p<0.05).</p><p><strong>Discussion: </strong>The PCDI outperforms traditional prognostic models by capturing PCD-immunemetabolic crosstalk. High-PCDI tumors demonstrate adaptive immune evasion despite an elevated checkpoint molecule expression, suggesting therapeutic potential for combined MAPK inhibitors and immunotherapy. Limitations include retrospective data and small validation cohorts.</p><p><strong>Conclusion: </strong>The PCDI provides a robust molecular framework for risk stratification and personalized therapy in invasive PitNETs. Future studies should validate its clinical utility and explore pancancer relevance.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"1-16"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Key Epigenetic Modification-Related Genes for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma and Cellular Validation.","authors":"Huizhen Zhang, Junjie Li, Heng Xu, ShiSong Zhang, Yunkun Lu, Sijie Feng","doi":"10.2174/0115665232432474251103064112","DOIUrl":"10.2174/0115665232432474251103064112","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) is a highly prevalent female malignancy. As the epigenomic characteristics of immune cells and cancer cells can serve as predictive indicators for the response to cancer immunotherapy, analysis of epigenetically modified genes (EpiGenes) could contribute to CESC treatment.</p><p><strong>Methods: </strong>The ssGSEA algorithm was employed to compute EpiGenes scores. Core genes that exhibited significant module association and a close correlation with EpiGenes scores were identified via the WGCNA package. Univariate Cox proportional hazards regression was performed on the core genes using the survival package, followed by gene set reduction via LASSO Cox regression. Ultimately, key genes were determined through multivariate Cox regression to establish a RiskScore model. Further, the optimal risk cutoff was determined using the survminer package to stratify CESC patients into high- and low-risk subgroups. For enrichment analysis, clusterProfiler and GSEA were utilized. Immune infiltration across risk groups was evaluated via ssGSEA, the MCPcounter algorithm, and the ESTIMATE algorithm. TIDE was employed to compare immunotherapeutic responses between the risk groups, while the pRRophetic software was utilized to predict patients' chemotherapeutic drug sensitivity. The biomarkers identified were validated by performing in vitro experiments.</p><p><strong>Results: </strong><i>CEP78, DOCK7, DPY19L4</i>, and <i>POM121</i> were identified by computational analyses as the key genes for CESC and further validated through <i>in vitro</i> experiments. Pathway enrichment analysis revealed predominant enrichment in immune-related pathways in the high-risk group, whereas the low-risk group was more enriched in energy and metabolic pathways. A significant negative correlation was observed between CD8+ T cell abundance and RiskScore, with higher ESTIMATEScores and StromalScores in high-risk patients. Notably, the high-risk group also demonstrated lower potential sensitivity to immunotherapy but more active responsiveness to a broader spectrum of chemotherapeutic agents.</p><p><strong>Discussion: </strong>Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that module genes are significantly enriched in cell cycle regulatory pathways, and these genes, in conjunction with Human Papillomavirus (HPV) infection-induced cell cycle dysregulation, jointly participate in CESC pathogenesis, providing a mechanistic basis for understanding the disease.</p><p><strong>Conclusion: </strong>This study provided novel theoretical evidence for immunotherapy and chemotherapy selection in the management of CESC.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":"1-13"},"PeriodicalIF":3.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145602792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}