Comparative and Functional Genomics最新文献

{"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}

{"title":"Deciphering Pleiotropic Single-Nucleotide Polymorphisms Governing Fertility–Milk Yield Trade-Offs in Dairy Cattle: A Genome-Wide Chromosomal Landscape Analysis","authors":"Heydar Ghiasi,&nbsp;Majid Khaldari,&nbsp;Reza Taherkhani,&nbsp;Navid Ghavi Hossein-Zadeh","doi":"10.1155/ijog/5167047","DOIUrl":"https://doi.org/10.1155/ijog/5167047","url":null,"abstract":"<p>Fertility and milk production in dairy cattle are economically significant traits, but they exhibit an unfavorable genetic correlation, making simultaneous improvement challenging. Identifying pleiotropic genes that influence both traits can provide valuable insights for genomic selection. This study aimed to identify common significant SNPs (CSSNPs) associated with both fertility and milk production traits and map these SNPs to pleiotropic genes, highlighting genomic regions with potential for simultaneous improvement of these traits. Significant SNPs for fertility (6336 SNPs) and milk production (6353 SNPs) were analyzed to identify 196 CSSNPs. These SNPs were mapped to 160 pleiotropic genes, and their distribution across cattle chromosomes (BTAs) was examined, focusing on key genomic regions. The highest number of CSSNPs (35) and pleiotropic genes (24) was identified on BTA6, while BTA14 harbored 21 pleiotropic genes. Several chromosomes, including BTA24 and BTA29, had no pleiotropic genes. In chromosome X, 4 CSSNPs and 3 pleiotropic genes were identified. This study identified critical genomic regions and pleiotropic genes associated with both fertility and milk production, providing insights into the genetic architecture of these traits. The findings highlight specific regions, particularly BTA6 and BTA14, which are promising targets for genomic selection. These results can inform breeding programs by enabling the development of strategies to simultaneously improve fertility and milk production in dairy cattle, optimizing productivity and sustainability.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/5167047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147614910","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":"Applications and Challenges of Epigenetic Signature Detection in the Diagnostic Genomics Laboratory–Current and Future Directions","authors":"Amy Harte","doi":"10.1155/ijog/6528661","DOIUrl":"https://doi.org/10.1155/ijog/6528661","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Epigenetic signature detection (ESD) identifies disease-associated DNA methylation patterns and offers valuable insights beyond traditional genomic testing. Episignatures are increasingly recognised for their diagnostic potential, particularly in rare and complex disorders where conventional sequencing falls short.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Main Body</h3>\u0000 \u0000 <p>Several approaches are used for ESD, ranging from cost-effective arrays to advanced sequencing methods. Methylation arrays and PCR remain accessible options, while whole-genome and 5-base sequencing offer greater resolution and integration with genomic data. Interpretation relies on robust reference datasets and bioinformatic tools, with machine learning aiding in classification accuracy. Clinically, ESD has proven valuable in diagnosing imprinting disorders, Mendelian epigenetic conditions and cancer subtypes—particularly central nervous system tumours. It also shows promise in variant classification and liquid biopsy applications. Emerging uses in pharmacogenomics and neuropsychiatric disorders are under investigation but require further validation. Despite its potential, implementation faces challenges including lack of standardisation, regulatory oversight and workforce training. Ethical concerns such as incidental findings, informed consent and data use must be carefully addressed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ESD is a promising complement to genomic testing, with the potential to enhance diagnostic precision across a range of conditions. Continued technological advancement, validation and collaborative efforts will be essential for its successful and responsible clinical adoption.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/6528661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147614936","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":"Identification of Key Genes in Acute Liver Failure via Analysis of Programmed Cell Death Patterns","authors":"Guangli Liu,&nbsp;Huili Wu,&nbsp;Wenxiang Shi,&nbsp;Chenjie Qiu","doi":"10.1155/ijog/4119010","DOIUrl":"https://doi.org/10.1155/ijog/4119010","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Acute liver failure (ALF) is a severe condition with high mortality, where programmed cell death (PCD) plays a critical yet not fully understood role. This study aimed to identify key PCD-related genes and explore their potential as biomarkers and therapeutic targets in ALF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three HBV–ALF microarray datasets (GSE14668, GSE38941, GSE62029) from GEO were integrated and analyzed. Differential expression analysis, protein–protein interaction (PPI) network construction, and functional enrichment were performed. Machine learning algorithms (LASSO and random forest) were used to identify hub genes. Immune infiltration was assessed via CIBERSORT and ssGSEA. Regulatory networks involving miRNAs and transcription factors (TFs) were constructed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 109 differentially expressed PCD genes were identified. TIMP1 and IL18 were consistently selected as hub genes by both CytoHubba and machine learning methods. These genes demonstrated high diagnostic accuracy and prognostic value in ALF. Immune infiltration analysis revealed significant associations with macrophage polarization. Functional enrichment linked TIMP1 and IL18 to immune and metabolic pathways. A miRNA–mRNA–TF regulatory network was constructed, with STAT3 identified as a key upstream regulator.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TIMP1 and IL18 are potential diagnostic biomarkers and candidate therapeutic targets for ALF, closely associated with immune infiltration and PCD processes. These findings provide new insights into the molecular mechanisms of ALF and support the development of targeted therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/4119010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147584955","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":"Multiomics Integration Reveals KRT16 as a UPR-Related Driver of Aggressive Tumor Behavior and Immunosuppression in Ovarian Serous Cystadenocarcinoma","authors":"Meng Yang,&nbsp;Peipei Zheng,&nbsp;Chan Meng,&nbsp;Weimin Wang","doi":"10.1155/ijog/4806618","DOIUrl":"https://doi.org/10.1155/ijog/4806618","url":null,"abstract":"<p>Ovarian serous cystadenocarcinoma (OV) remains a lethal malignancy with complex tumor microenvironment (TME) dynamics and heterogeneous therapeutic responses. Unfolded protein response (UPR) signaling has been implicated in tumor progression and therapy resistance, yet its role in OV remains underexplored. Leveraging single-cell RNA sequencing (scRNA-seq) data and bulk RNA-seq cohorts, we deciphered the cellular composition of the OV microenvironment and identified UPR-related molecular subtypes. Through integrative analysis, we pinpointed KRT16 as a key prognostic gene associated with adverse outcomes. High KRT16 expression correlated with distinct mutational profiles, altered immune infiltration, and reduced sensitivity to targeted agents such as PD0325901 and dasatinib. Our findings nominate KRT16 as a novel biomarker and potential therapeutic target in OV, linking UPR activity to tumor aggression, cytoskeletal remodeling, immune modulation (including myeloid-derived suppressor cell recruitment), and therapy resistance.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/4806618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147579684","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":"FTO Acts as a Suppressor Gene to Inhibit the Translation of KDM5A mRNA by Demethylating m6A Modifications in Lung Adenocarcinoma","authors":"Wen Zhao,&nbsp;Chen Zhu,&nbsp;Ning Wang,&nbsp;Bin Wu,&nbsp;Xuelin Lu,&nbsp;Ye Xu","doi":"10.1155/ijog/4209006","DOIUrl":"https://doi.org/10.1155/ijog/4209006","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background:</h3>\u0000 \u0000 <p>Fat mass and obesity-associated (FTO) protein, an m6A RNA demethylase, plays diverse roles in cancer, but its function in lung adenocarcinoma (LUAD) remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods:</h3>\u0000 \u0000 <p>TCGA data analysis, clinical samples, and in vitro assays were used to assess FTO expression and function. Mechanistic studies, including RIP, meRIP, luciferase reporter, FISH, and ChIP assays, were performed to explore FTO-mediated regulation of KDM5A and downstream PTEN/PI3K/Akt signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results:</h3>\u0000 \u0000 <p>FTO was significantly downregulated in LUAD and associated with poor prognosis. Overexpression of FTO inhibited LUAD cell proliferation, invasion, and EMT. Mechanistically, FTO suppressed KDM5A protein translation by demethylating m6A sites, impairing YTHDF1-mediated recognition. Reduced KDM5A expression increased PTEN transcription via elevated H3K4me3, leading to PI3K/Akt inactivation. Rescue experiments confirmed KDM5A overexpression reversed the effects of FTO.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions:</h3>\u0000 \u0000 <p>FTO inhibits LUAD progression through an m6A-dependent FTO/YTHDF1/KDM5A/PTEN axis. These findings establish FTO as a tumor suppressor and potential therapeutic target in LUAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/4209006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147585293","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 Neurotrophic Factor–Related Gene Signature Predicts Prognosis and Immunotherapy Response in Colorectal Cancer","authors":"Xu-Yang Zuo,&nbsp;Yu Xia,&nbsp;Jia Liu,&nbsp;Xi Chen,&nbsp;Xue-Song Yan,&nbsp;Jia-Yi Zhang,&nbsp;Zi-Hao Xu,&nbsp;Jing-Ri Wang,&nbsp;Ying-Xu Sun,&nbsp;Zhuo-Xin Cheng,&nbsp;Yan-Li Zhu","doi":"10.1155/ijog/6519791","DOIUrl":"https://doi.org/10.1155/ijog/6519791","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;Neurotrophic factors (NFs) are critical for neural development, survival, and function. Emerging evidence suggests their involvement in tumorigenesis, progression, and therapy resistance. However, their comprehensive prognostic and therapeutic implications in colorectal cancer (COAD) remain largely unexplored.&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 systematically identified neurotrophic factor-related genes (NFRGs) and constructed a prognostic signature using transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO, dataset GSE39582) cohorts. Differential expression analysis and functional enrichment (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]), univariate, and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analyses were employed to develop a risk model. The model was validated for its ability to stratify patients by overall survival (OS), tumor microenvironment (TME), immune cell infiltration, response to immunotherapy, and chemosensitivity. Single-cell RNA sequencing (scRNA-seq) analysis and cell–cell communication inference were performed to validate the findings at a cellular 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;A robust 12-gene NFRG signature was established, effectively stratifying COAD patients into high- and low-risk groups with distinct OS. The high-risk group was characterized by enriched epithelial–mesenchymal transition (EMT) pathways, an immunosuppressive TME with increased cancer-associated fibroblast (CAF) and M2 macrophage infiltration, and a higher tumor mutation burden. The risk score served as an independent prognostic factor and correlated with advanced clinical stages, BRAF mutation status, and Consensus Molecular Subtypes (CMS). Critically, high-risk patients exhibited higher TIDE scores, increased CD274 (PD-L1) expression, and greater potential response to immune checkpoint blockade, alongside reduced sensitivity to 5-fluorouracil. scRNA-seq analysis pinpointed epithelial cells as the primary source of NFRG expression, and CellChat analysis revealed enhanced intercellular communication, particularly involving Schwann cell–derived SPP1 signaling, in high-risk tumors.&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;We established and validated a novel NFRG-based risk model that accurately predicts prognosis, delineates the immune landscape, and informs therapeutic strategies in COAD. This signature presents a promising biomarker for personalized treatment stratification, potentially guiding im","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/6519791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147566236","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":"Machine Learning Integration of Multiomics Data Reveals RNA Modification–Driven Inflammation–Immune Interplay and Predicts Immunotherapy Response in Cervical Cancer","authors":"Pengyan Zhang,&nbsp;Xiaoying Li,&nbsp;Jing Cao,&nbsp;Liping Gong,&nbsp;Ling Wang,&nbsp;Litao Sun,&nbsp;Yaoting Wang","doi":"10.1155/ijog/6458805","DOIUrl":"https://doi.org/10.1155/ijog/6458805","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The interplay between inflammation, immunity, and RNA modification (RM) in the tumor microenvironment (TME) of cervical cancer (CC) remains poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We performed integrated analysis of single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), and bulk RNA-seq data. A comprehensive computational framework, encompassing 101 machine learning algorithms, was used to construct a consensus machine learning–derived RNA methylation signature (CMDRMS). This signature was evaluated for its prognostic value, association with immune cell infiltration, inflammatory profiles, and response to immunotherapy and pharmacotherapy. Key findings were validated through RT-qPCR, immunofluorescence, and structural modeling via AlphaFold3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>scRNA-seq and ST revealed significant enrichment of RM regulators within tumor epithelial cells and specific immune subsets in the TME. The CMDRMS, comprising four hub genes (CBLLI, LARPI, NUDT3, and METTL16), effectively stratified patients into high- and low-risk groups according to the mean CMDRMS score. The high-CMDRMS group exhibited poorer overall survival, an inflamed TME with enhanced immune cell infiltration, yet a paradoxically diminished response to PD-1/CTLA-4 blockade, suggesting an immunosuppressive phenotype. Conversely, these patients showed potential sensitivity to PD-L1 therapy. Drug sensitivity analysis identified 48 agents with greater efficacy in the low-CMDRMS group. Pseudotime analysis indicated that core CMDRMS genes, particularly NUDT3, were upregulated in later differentiation stages. Experimental validation confirmed the overexpression of NUDT3 in CC tissues and cell lines, correlating with advanced clinical stages. Crucially, NUDT3 demonstrated significant coexpression and predicted structural interaction with PD-L1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study underscores the critical role of RM in shaping the inflammation–immune interplay within the CC TME and provides a novel prognostic biomarker (CMDRMS) for CC and a potential therapeutic target (NUDT3) for reversing immunotherapy resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/6458805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565837","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":"S100A9 Integrates Autophagic Deficiency With Immunopathology and Latanoprost Responsiveness in Primary Open-Angle Glaucoma","authors":"Lili Hu,&nbsp;Shaoxin Pan,&nbsp;Gong Chen,&nbsp;Min Lei,&nbsp;Ming Ai,&nbsp;Xiangyun Lv,&nbsp;Haoning Pan,&nbsp;Peng Wang,&nbsp;Rui Chang","doi":"10.1155/ijog/3168725","DOIUrl":"https://doi.org/10.1155/ijog/3168725","url":null,"abstract":"<p>Primary open-angle glaucoma (POAG) is a progressive optic neuropathy that leads to irreversible vision loss, primarily due to dysfunction of the trabecular meshwork (TM). Although impaired autophagy has been implicated in POAG pathogenesis, its molecular drivers remain poorly defined. This study systematically investigated autophagy-related genes (ATGs) in TM tissue from POAG patients. Transcriptomic datasets (GSE4316 and GSE27276) were analyzed to identify differentially expressed genes (DEGs). A curated list of autophagy-related genes (ATGs) from HADb and GeneCards was intersected with DEGs to identify differentially expressed ATGs (DEATGs). Functional analyses included Gene Ontology (GO) and KEGG pathway enrichment, protein–protein interaction (PPI) network construction, hub gene identification, immune cell infiltration profiling via single-sample gene set enrichment analysis (ssGSEA), and molecular docking to evaluate predicted interactions between latanoprost and hub proteins. A total of 990 DEGs were identified, including 15 DEATGs. Among these, S100A8 and S100A9 emerged as hub genes, exhibiting strong functional similarity and central roles within the PPI network. Enrichment analysis revealed significant involvement in autophagy regulation, tyrosine metabolism, and oxidative phosphorylation. Notably, molecular docking predicted high-affinity binding between latanoprost and S100A9. Immune profiling demonstrated significant alterations in both innate and adaptive immune cell populations, including a strong positive correlation between S100A9 expression and Th2 cell abundance. These findings suggest that S100A9 may act as a central regulator linking autophagy deficiency to immune dysregulation in POAG. Its predicted interaction with latanoprost highlights a potential molecular mechanism for pharmacologic modulation of TM homeostasis, supporting the therapeutic value of targeting S100A9-mediated autophagy–immune crosstalk in intraocular pressure control.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/3168725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565035","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 Mendelian Randomization and Pathomics Analysis Using Expression Quantitative Trait Loci and Genome-Wide Association Study Data Identifies Mismatch Repair Genes as Prognostic Biomarkers in Gastric Adenocarcinoma","authors":"Yingqiao Zhang,&nbsp;Dan Li,&nbsp;Yuyao Jin,&nbsp;Wenjuan Zhao,&nbsp;Pengyu Guo,&nbsp;Ziqi Wang,&nbsp;Xinyu Zhu,&nbsp;Zhenqi Ma,&nbsp;Lin Sui,&nbsp;Yanmeng Liang,&nbsp;Yang Liu,&nbsp;Xiushi Zhang","doi":"10.1155/ijog/2686529","DOIUrl":"10.1155/ijog/2686529","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mismatch repair (MMR) genes are implicated in stomach adenocarcinoma (STAD). This study assessed their causal role in STAD, prognostic value, and developed a histopathology-based model to predict MutS homolog 2 (MSH2) expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using data from the IEU OpenGWAS database, five Mendelian randomization (MR) models evaluated causal links between MMR genes and gastric cancer (GC). Prognostic relevance was assessed via survival analysis. A random forest model using TCGA hematoxylin and eosin–stained images was trained to predict MSH2 expression. Biological insights were explored via pathomics score, gene set enrichment analysis (GSEA), immune infiltration, and tumor mutational burden (TMB).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MR analysis identified MLH1 and PMS2 as risk genes, while MSH2 had a protective effect. Cox regression confirmed MSH2 as an independent protective factor (HR = 0.690, 95% CI: 0.487–0.977, <i>p</i> &lt; 0.05). The pathomics model predicted MSH2 expression with an AUC of 0.811. A comparison of high- and low-survival-probability (SP) groups showed differentially expressed genes, including SFRP4. The high-SP group had elevated TMB and TP53 mutation frequency.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MMR genes, especially MSH2, are critical in STAD development and prognosis. The image-based model effectively predicts MSH2 expression, supporting the integration of genomic and histopathologic data for personalized GC care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12968895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432695","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}