Comparative and Functional Genomics最新文献

{"title":"A Multiomics and Bioinformatics Analysis of the Role and Mechanism of CNKSR1 in Ovarian Cancer Progression","authors":"Weili Zhu,&nbsp;Yimin Huang,&nbsp;Jiayue Huang,&nbsp;Jianguo Wang,&nbsp;Sijia Shen","doi":"10.1155/ijog/1546020","DOIUrl":"10.1155/ijog/1546020","url":null,"abstract":"<p>This study aims to utilize multiomics and bioinformatics techniques to investigate the expression of the connection enzyme inhibitor Ras1 1 (CNKSR1) in ovarian cancer (OC) and its mechanism of action in the processes of tumor proliferation, invasion, and metastasis. Transcriptome sequencing was performed on paired cancerous and normal ovarian tissues from three OC patients. Differentially expressed genes (DEGs) mRNAs were analyzed using “limma”, and key DEGs were identified through LASSO and random forest (RF) methods. <i>CNKSR1</i> expression in OC tissues was assessed via quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. Gene Ontology (GO) enrichment analysis was conducted utilizing the Database for Annotation, Visualization, and Integrated Discovery (DAVID), and CancerSEA was employed to assess the functional status of <i>CNKSR1</i> in OC. Also, the proliferation of cells, their invasion, and migration were evaluated. ChEA3 and hTFtarget were used to identify potential transcription factors targeting <i>CNKSR1</i>. The predicted factors were validated by Western blot analysis in OC cells overexpressing <i>CNKSR1</i> or in OC cells with the <i>CNKSR1</i> knockdown. Compared to normal tissues, 78 genes were downregulated, and 101 were upregulated in OC. LASSO and RF analyses identified <i>CNKSR1</i> as a vital gene positively correlated with the progression of OC, which was then experimentally validated. <i>CNKSR1</i> upregulation promoted the OC cells’ proliferation, their invasion, and migration, while its silencing inhibited these processes. Analysis of the ChEA3 and hTFtarget databases, as well as Western blot analysis, suggested that <i>CNKSR1</i> may drive epithelial-mesenchymal transition (EMT) by upregulating snail and ZEB1 expression. <i>CNKSR1</i> serves a significant role in promoting the growth and progression of OC. It enhances OC cells’ metastatic and invasive abilities by regulating the EMT mediated by the transcription factors Snail and ZEB1.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Cell-Mediated Retinoblastoma Development: Genetic and Molecular Mechanisms","authors":"Xinyang Hu,&nbsp;Jingqiu Li,&nbsp;Jinhong Li,&nbsp;Wenxuan Chen,&nbsp;Haibo Zhang,&nbsp;Dan Li,&nbsp;Ming Zhu,&nbsp;Liang Pang,&nbsp;Siqi Fan,&nbsp;Suolang Yangzong,&nbsp;Ciren Deji,&nbsp;Dongwei Liu","doi":"10.1155/ijog/6303747","DOIUrl":"10.1155/ijog/6303747","url":null,"abstract":"<p>Retinoblastoma (RB) is the most prevalent malignant tumor that originates within the eye in children, occurring at a frequency of around 1:20,000 to 1:15,000. RB typically occurs when both alleles of the retinoblastoma 1 (RB1) gene are deactivated. RB is associated with variations in the tumor suppressor gene RB1 and is inherited in an autosomal recessive manner, operating at the genetic level. Variation in RB1 occurs only when two alleles of the RB1 gene are mutated. The mechanism by which immune cells mediate RB1 to affect RB is still unclear. Using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics, we investigated the relationship between immune cells and RB1 proteins. Our goal was to understand their potential role in the development of RB in offspring. The analysis of alterations in RB tissue cells and potential molecular mechanisms was conducted using single-cell RNA sequencing data. The research revealed the presence of 28 immune cells linked with RB1. These variables might potentially impact the likelihood of RB in children by altering the expression of the RB1 gene in their parents. Furthermore, we found differential gene expression in different cells of the RB tissue. EZH2, UBLCP1, and HKDC1 overlapped with the identified instrumental variables (IVs) of immune cells to investigate potential molecular mechanisms by which immune cells participate in RB processes.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13063122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Analysis of Telomere-Related Genes Reveals Prognostic Signatures in Laryngeal Cancer","authors":"Yesong Cheng,&nbsp;Yingjie Zhao,&nbsp;Lin He,&nbsp;Dingqiang Huang,&nbsp;Feipeng Zhao,&nbsp;Xiangyang Shi,&nbsp;Wensong Tang,&nbsp;Yi Liu,&nbsp;Wujun Zou,&nbsp;Xiaolong Tang,&nbsp;Yi He","doi":"10.1155/ijog/5301600","DOIUrl":"10.1155/ijog/5301600","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Laryngeal cancer (LC) is a common malignant tumor. Telomere-related genes (T-RGs) play critical roles in cellular senescence and carcinogenesis, but their prognostic relevance in LC remains to be fully elucidated. Therefore, exploring the prognostic genes related to telomeres in LC is important.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Public retrospective datasets TCGA-HNSC and T-RGs were used to identify candidate genes by intersecting differentially expressed genes with T-RGs. Key analytical approaches, including machine learning algorithms and univariate Cox regression, were applied to identify prognostic genes and construct a prognostic model. A nomogram was developed to assess the prognostic value for LC based on overall survival. Disease samples were classified into high-risk and low-risk groups, and subsequent analyses included immune infiltration, immune checkpoint expression, and related evaluations. Experimental validation of prognostic genes was performed through RT-qPCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 314 candidate genes were obtained from 8961 differentially expressed genes. Four key prognostic genes (CHTF18, FANCG, NR5A1, and XRCC3) were identified. The constructed risk score model retained consistent predictive accuracy in both the training and validation datasets, with AUCs ranging from approximately 0.61 to 0.9. Enriched activated immune cells were detected in the low-risk group through immune microenvironment analysis, whereas immune suppression–related features were identified in the high-risk group, accompanied by a reduced tumor mutational burden that was detected. Finally, preliminary validation using RT-qPCR in a limited cohort of clinical samples indicated that the expression trends of three prognostic genes were elevated in LC tissues, showing concordance with the bioinformatic findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identified four key prognostic T-RGs (CHTF18, FANCG, NR5A1, and XRCC3) and constructed a corresponding prognostic model for LC. Our analyses further suggest a potential link between telomere maintenance mechanisms and the tumor immune microenvironment, which may influence patient outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13059680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Cross-Tissue Multiomics Analysis Reveals the Protective Role of TGFBR3 in Postmenopausal Osteoporosis","authors":"Yimin Liu,&nbsp;Chenxu Xie,&nbsp;Kaiwen Yang,&nbsp;Zixuan Liu,&nbsp;Runtong Liu,&nbsp;Xiaoli Hou,&nbsp;Lei Xing,&nbsp;Jingyuan Gao,&nbsp;Qiangqiang Lian,&nbsp;Yunpeng Hu,&nbsp;Yongheng Wang,&nbsp;Liu Zhang,&nbsp;Faming Tian","doi":"10.1155/ijog/6364895","DOIUrl":"10.1155/ijog/6364895","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Postmenopausal osteoporosis (PMO) develops as a result of pathological cross-tissue interactions. However, current experimental paradigms are constrained by their single-tissue focus, hindering efforts to discover systemwide regulatory genes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We aimed to discover conserved genetic regulators of PMO by integrating cross-tissue transcriptomic profiles in humans and to characterize their biological functions via combined genetic epidemiology and experimental studies using integrated analytical strategies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our analytical framework encompassed transcriptome profiles from human peripheral blood mononuclear cells, bone marrow, and bone tissue. We adopted a tiered strategy involving differential expression analysis, weighted gene coexpression network construction, and machine learning with 108 algorithm combinations for candidate gene selection. A two-sample Mendelian randomization was used to inform causal gene–disease relationships, while the key results were validated in an ovariectomized mouse model of osteoporosis. Mechanistic studies included single-cell transcriptomics, functional enrichment, and immune microenvironment profiling.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cross-tissue analysis identified 97 consistently dysregulated genes between tissues, which were further refined to 64 high-confidence candidates. TGFBR3 was significantly protective against PMO (IVW OR = 0.675, 95% CI: 0.466–0.977, &lt;i&gt;p&lt;/i&gt; = 0.037). Osteoporotic mice exhibited considerable downregulation of TGFBR3 expression, which was positively correlated with bone mineral density and mechanical properties as well as bone formation markers and negatively correlated with resorption markers. Cellular localization showed enrichment of TGFBR3 in bone marrow mesenchymal stem cells and T cells from human and mouse bone marrow. Functional analyses suggested that its protective effects involve the modulation of osteogenic differentiation pathways and regulation of the immune microenvironment.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This is the first study to identify TGFBR3 as a novel cross-tissue protective regulator of PMO. Our integrated approach covering genomic discovery, causal inference, and experimental validation offers strong support to the hypothesis that TGFBR3 deficiency constitutes a fundamental feature of PMO pathogenesis, while shedding li","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Analysis Based on the Cancer-Immunity Cycle Identifies a Novel Immunosuppressive Subtype of Bladder Cancer","authors":"Zexun Deng,&nbsp;Yifan Li,&nbsp;Yuyong Shen,&nbsp;Ming Zhou","doi":"10.1155/ijog/9720283","DOIUrl":"10.1155/ijog/9720283","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Immune checkpoint blockade (ICB) has reshaped the approach to treating a broad spectrum of cancers, including bladder cancer (BLCA). However, a substantial fraction of BLCA patients still exhibit resistance despite high programmed death-ligand 1(PD-L1) expression in the tumor. Consequently, it is imperative to characterize the tumor immunosuppressive microenvironment (TME) and ascertain key biomarkers associated with immune evasion in order to stratify patients according to their propensity for immunotherapy resistance.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A retrospective analysis of RNA sequencing data sourced from 403 BLCA samples was conducted during the course of our experimental research. Our research team employed weighted gene coexpression network profiling (WGCNA) and machine learning models to uncover tumor-immune cycle-associated genes that are tightly linked to BLCA. Unsupervised clustering was implemented to explore the tumor microenvironment-associated gene expression profiles. Subsequently, in turn, we drew correlations between these expression signatures and a group of T cell exhaustion indicators, receptors, and immunotherapy responsiveness to further categorize them. Finally, a set of experiments were executed to verify the putative role of the core gene BIRC5 in BLCA at the experimental level.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Through comprehensive analysis, BIRC5, HSPA12A, and CXCL12 were identified as hub genes. Additionally, based on the molecular expression profiles of these three hub genes, BLCA patients were stratified into distinct subgroups. Simultaneously, this classification was correlated with the immune microenvironment landscape and established the exhausted immune class (EIC)—a novel subtype with high PD-L1 expression, exhausted T cell markers, and immunosuppressive cytokines—in BLCA patients. Finally, we confirmed that BIRC5 exhibited high expression levels in BLCA and was involved in modulating the malignant proliferation, migratory activity, and invasive behavior of BLCA cells in vitro.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The investigative group validated the oncogenic activity of BIRC5, a gene correlated with the tumor-immune cycle. Additionally, our research team has identified a novel molecular subtype of BLCA that exhibits high expression of PD-L1 but may potentially exhibit resistance to ICB therapy. These findings offer valuable insights into comprehensively characterizing the immunosuppressive tumor microenvironment in BLCA and present opportuniti","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Single-Cell Transcriptomics and Network Pharmacology Analysis of Xiao Qing Long Tang in Pediatric Cough-Variant Asthma","authors":"Mingming Cui,&nbsp;Qianqian Li,&nbsp;Xue Ding,&nbsp;Mengjie Zhou,&nbsp;Ximeng Lou,&nbsp;Lihong Xia","doi":"10.1155/ijog/2536457","DOIUrl":"10.1155/ijog/2536457","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Pediatric cough-variant asthma is characterized by chronic airway inflammation and epithelial dysfunction driven by complex cellular interactions and molecular regulatory networks. Understanding the cellular heterogeneity and molecular mechanisms underlying pediatric asthma pathogenesis remains challenging. Single-cell RNA sequencing (scRNA-seq) provides unprecedented resolution to dissect the molecular landscape of asthmatic airways at the individual cell level.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We performed a comprehensive single-cell transcriptomic analysis of airway epithelial tissues from pediatric asthma patients using the 10x Genomics platform. Following stringent quality control, dimensionality reduction analysis, and cell clustering, we identified distinct cell populations and characterized their molecular signatures. Developmental trajectory analysis was performed using the Monocle algorithm, and functional enrichment analysis was conducted to elucidate biological pathways. Additionally, network pharmacology was employed to explore the multitarget mechanisms of the traditional Chinese medicine formula Xiao Qing Long Tang (XQLT) in treating asthma.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We successfully constructed a single-cell atlas of pediatric asthma airway epithelium, identifying seven major cell subtypes: eosinophil cells, basal cells, ciliated cells, goblet cells, club cells, ionocyte cells, and deuterosomal cells. High-resolution analysis revealed 23 distinct macrophage subpopulations (M1–M23) with unique transcriptional profiles. Key genes including KRT16, CXCL5, MMP10, ADAM12, and MALAT1 showed cell type–specific expression patterns. Pseudotime trajectory analysis revealed aberrant differentiation pathways from basal cells to specialized epithelial cells. Functional enrichment analysis highlighted inflammatory responses, immune system processes, and tissue remodeling as predominant biological processes in asthmatic airways. The network pharmacology analysis further identified 124 common targets, revealing that XQLT exerts multicomponent, synergistic therapeutic effects through core hubs such as NFE2L2 and NOS2.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This comprehensive single-cell transcriptomic atlas provides novel insights into the cellular heterogeneity and molecular mechanisms of pediatric asthma. The identification of cell type–specific gene expression patterns and developmental trajectories offers potential targets for precision therapeutic interventions.&lt;/p&gt;\u0000 ","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Flooding Challenges, Causes, and Mitigation Strategies in Rice","authors":"Abdoul-Razak Oumarou Mahamane,&nbsp;Junior S. Kamara,&nbsp;Moise Hubert Byiringiro,&nbsp;Alpha Sow","doi":"10.1155/ijog/7576298","DOIUrl":"10.1155/ijog/7576298","url":null,"abstract":"<p>Flooding is a dominant constraint to rice production in lowland and floodplain ecosystems, where stress intensity, timing, and duration vary widely across agroecological zones. This review synthesizes current knowledge on flooding typologies affecting rice, including anaerobic germination failure, flash flooding, stagnant flooding, and deep-water submergence, and critically examines how rice plants respond at physiological, anatomical, and molecular levels. We integrate evidence on key adaptive mechanisms, including anaerobic metabolism during germination, SUB1-mediated quiescence under short-term submergence, SNORKEL-driven internode elongation in deep-water environments, aerenchyma development, leaf gas films, and antioxidant defense systems. Particular emphasis is placed on the genetic architecture underpinning these responses, highlighting the successes and limitations of the SUB1 locus and the necessity of multitrait pyramiding to address prolonged, deep, or sequential flooding events. Drawing on case studies from Africa and Asia, the review demonstrates that flooding impacts are strongly context-specific, shaped by rainfall variability, hydrology, soil properties, and water management infrastructure, with disproportionate socioeconomic consequences for smallholder farmers. We argue that reliance on single-gene solutions is insufficient under climate change scenarios that intensify flood unpredictability. Instead, resilient rice systems require an integrated strategy combining stress-tolerant varieties, adaptive crop and nutrient management, and climate-informed decision-making. By consolidating physiological insights, breeding advances, and regional flood dynamics, this review provides a targeted framework for developing rice varieties and management options tailored to diverse flooding regimes, with direct implications for food security in flood-prone regions.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Prognostic Biomarkers in Lung Adenocarcinoma: Strategic Integration of Metabolic Subtyping and Ubiquitination Pathways","authors":"Yang Yang,&nbsp;Jun Yang,&nbsp;Deyang Liu,&nbsp;Xiaolu Fang,&nbsp;Baishan Liu","doi":"10.1155/ijog/5660376","DOIUrl":"https://doi.org/10.1155/ijog/5660376","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lung adenocarcinoma (LUAD), the most prevalent form of nonsmall cell lung cancer, poses significant diagnostic and therapeutic challenges due to its high mortality rate and complex pathophysiology. Despite advances in understanding LUAD’s molecular underpinnings, existing biomarkers are insufficient for personalized treatment, highlighting a critical need for innovative diagnostic and prognostic tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>By systematically analyzing data from the TCGA database, we identified three distinct metabolic subtypes of LUAD and conducted in-depth metabolic and immune profiling on these metabolic subtypes. This study employs extensive bioinformatics methodologies, including weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression, to discover and validate key genetic markers that impact LUAD prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings indicate that specific genes, such as SELK, C4orf27, PRDM2, FOSL2, and CHCHD4, play crucial roles in LUAD progression by intricately regulating ubiquitination pathways vital to tumor behavior. These genes are instrumental in orchestrating the delicate balance between ubiquitination and deubiquitination, essential for maintaining cellular homeostasis and regulating protein degradation pathways critical in oncogenesis. Notably, these genes exhibit a strong correlation with poor survival outcomes, highlighting their potential as therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The unique value of this research lies in the novel integration of metabolic, immune, and genomic data to elucidate LUAD’s heterogeneity. By pinpointing critical genetic drivers of LUAD and their broader biological impacts, this study significantly enhances our capability to predict and alter the disease’s trajectory, ultimately paving the way for advancements in targeted therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/5660376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the Regulatory Mechanism of Huazhuo Runzao Jiangqi Formula on Esophageal Cancer Utilizing Network Pharmacology, Molecular Docking, and In Vivo and In Vitro Experiments","authors":"Yun He,&nbsp;Huan-Fang Fan,&nbsp;De-Hui Li,&nbsp;Zi-Hui Liu,&nbsp;Yi-Ting Gu,&nbsp;Chang-Hui Han,&nbsp;Pan Ma,&nbsp;Na Guo,&nbsp;Xiao Wang,&nbsp;Yan Han","doi":"10.1155/ijog/2703091","DOIUrl":"https://doi.org/10.1155/ijog/2703091","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Esophageal cancer, a common digestive malignant neoplasm globally, poses significant health risks. Huazhuo Runzao Jiangqi (HRJ) formula, modified from the classic “Qige Powder” with additions and reductions, has shown clear efficacy in treating esophageal cancer and precancerous lesions in clinical practice and preliminary studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To explore HRJ’s antiesophageal cancer efficacy and mechanism via component identification, network pharmacology, molecular docking, and in vivo/in vitro tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>UHPLC-Q-Orbitrap HRMS analyzed HRJ’s chemical constituents. Network pharmacology identified target proteins and signaling pathways for esophageal cancer, with high-score proteins selected for molecular docking to confirm possible mechanisms. <i>In vivo</i>, tumor proliferation in nude mice was monitored; hematoxylin–eosin (HE) and immunohistochemistry were used to assess the effect of HRJ on tumor pathological characteristics, proliferation level, and autophagy level. <i>In vitro</i>, the CCK-8 assay evaluated HRJ’s effect on TE1 cell proliferation; cell migration and invasion assays were performed to observe HRJ’s effect on cell migration and invasion abilities; MDC staining examined autophagosomes; and Western blot and qRT-PCR analyzed PI3K/Akt/mTOR-related protein and gene expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>It was determined that HRJ contains 46 chemical constituents. Network pharmacology study suggested that the PI3K/Akt/mTOR signaling pathway may be pivotal in the mechanism of HRJ for treating esophageal cancer. In vivo and in vitro studies demonstrated that HRJ exerts an inhibitory effect on the proliferation, migration, and invasion of esophageal cancer. It can enhance the protein and gene expressions of Beclin1, Atg5, and PTEN via modulating the PI3K/Akt/mTOR signaling pathway, therefore promoting autophagy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HRJ activates autophagy via the PI3K/Akt/mTOR pathway, modulates key autophagy proteins, and inhibits esophageal cancer progression, providing a novel complementary therapy approach.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/2703091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147579804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aggrephagy Reshapes Tumor Microenvironment in Laryngeal Squamous Cell Carcinoma: Insights From Single-Cell Transcriptomics","authors":"Hui-min Xu,&nbsp;Ke-xin Ma,&nbsp;Shu-zheng Wang,&nbsp;Hao Wu,&nbsp;Hao-sheng Ni","doi":"10.1155/ijog/3789337","DOIUrl":"https://doi.org/10.1155/ijog/3789337","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The tumor microenvironment (TME) plays a crucial role in the development and progression of laryngeal squamous cell carcinoma (LSCC). However, the mechanisms by which aggrephagy reshapes the TME remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data of LSCC were obtained from the TCGA and GEO databases. Seurat and Monocle2 packages were employed for cell clustering and pseudotime trajectory analysis. SCENIC package was used to predict key transcription factors. The CellChat package was used to evaluate intercellular communication, and the GSVA method was applied to calculate signature scores across bulk RNA-seq datasets. The clinical significance of aggrephagy-associated subpopulations was assessed through survival analysis. Immunofluorescence staining was performed to evaluate TUBA1B expression and the infiltration of B cells and T cells in tumor tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The LSCC TME was mostly made up of epithelial cells, T/B lymphocytes, and myeloid cells. The TUBA1B + MaligEpi subpopulation of malignant epithelial cells had the highest level of stemness and was linked to a poor prognosis. The TUBA1B + subset of B cells showed impaired function, while the VIM + subset was able to present antigens. The HSP90AA1+ subset of macrophages demonstrated high inflammatory activity and was linked to TNF/NF-κB signaling. Cell communication analysis showed that VIM+ and TUBA1C + malignant epithelial cells and CD8+ T cells interacted strongly with each other. This could be a way for the immune system to be suppressed. TUBA1B was also highly expressed in several types of cancer and was linked to poor prognosis. B cell and T cell immune infiltration was accompanied by high TUBA1B expression, as confirmed by immunofluorescence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Aggrephagy is a key driver in TME remodeling in LSCC, highlighting TUBA1B as a promising prognostic biomarker and potential therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/3789337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147585167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}