Comparative and Functional Genomics最新文献

{"title":"IER3 Promotes Malignant Progression of Colorectal Cancer Through the NF-κB Pathway","authors":"Zhigang Wei,&nbsp;Yinyi Luo,&nbsp;Yupeng Zhang,&nbsp;Qingxing Huang,&nbsp;Jianhang Shao,&nbsp;Yingying Zhang,&nbsp;Yuqi Zhang,&nbsp;Zhimin Wang,&nbsp;Chaojie Liang,&nbsp;Zhiyong Lai,&nbsp;Yongping Cui","doi":"10.1155/ijog/8379666","DOIUrl":"10.1155/ijog/8379666","url":null,"abstract":"<p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, primarily due to metastatic progression and an immunosuppressive tumor immune microenvironment (TIME). The stress-responsive gene IER3 is found to be dysregulated in multiple cancers. Currently, its functional role in CRC pathogenesis and immune modulation remains poorly understood. Here, using integrated single-cell RNA sequencing (scRNA-seq) of clinical samples, we identify a distinct IER3-expressing malignant subpopulation associated with aggressive disease and poor prognosis. Functional studies demonstrate that IER3 drives CRC proliferation, invasion, and metastatic capacity both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, IER3 activates the TNF-<i>α</i>/NF-<i>κ</i>B signaling pathway, thereby enhancing the expression and phosphorylation of RELA/p65. Moreover, IER3⁺ malignant cells reshape the TIME into an immunosuppressive state by altering immune cell infiltration and promoting communication via the FN1–CD44 axis. High IER3 expression correlates with reduced response to immune checkpoint blockade (ICB) and distinct drug sensitivity profiles. Together, these findings confirm that IER3 is a dual critical mediator of CRC progression and immune escape, highlighting its potential as a therapeutic target and biomarker for personalized treatment strategies.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12859389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105354","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":"Multi-Omics Evidence Based on Spatial Transcriptomics Data Reveals the Therapeutic Value of Copper Death Genes in Glioblastoma","authors":"Zhaoliang Xue,&nbsp;Zhengfei Song,&nbsp;Lianjie Mo,&nbsp;Shuxu Yang","doi":"10.1155/ijog/6453352","DOIUrl":"10.1155/ijog/6453352","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cuprotosis is an emerging form of copper-dependent programmed cell death, while low-grade gliomas (LGGs) represent a common subtype of primary brain tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Datasets from The Cancer Genome Atlas and TargetScan were utilized to identify cuprotosis-related microRNAs (CRMs). Univariate Cox and Lasso regression analyses identified CRMs linked to prognostic outcomes. Prognostic profiles for patients with LGG were constructed using multivariate Cox regression and validated for risk stratification in the CGGA external validation cohort. The study examined clinical features, mutational status, immune cell infiltration, signaling pathways, and immune checkpoint expression across different risk groups. Functional experiments assessed the biological significance of key model genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seven CRMs significantly associated with LGG prognosis were identified. The correlation between the CRM signature and poor prognosis in high-risk LGG cases was validated through Kaplan–Meier survival analysis, yielding a one-year area under the curve (AUC) of 0.849, indicating strong predictive accuracy. Risk scores were linked to 1p/19q co-deletion, IDH mutation, and tumor grade, with the model outperforming traditional clinicopathological criteria. Molecular enrichment analyses, including Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), revealed significant associations between high-risk subgroups and pathways related to tumorigenesis and immune dysregulation. Increased tumor mutational burden and elevated IC expression were noted in high-risk cohorts. Furthermore, miR-93-5p was validated as a critical gene, with its disruption leading to significant reductions in GBM cell proliferation, migration, and invasion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The novel CRM signature enhances the prognostic landscape for patients with LGG, offering a new framework for evaluating immunotherapeutic efficacy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12854168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105348","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":"Design and Validation of a Predictive Model for Hepatocellular Carcinoma Based on Genes With Differential Expression Driven by DNA Methylation","authors":"Geyang Hu,&nbsp;Liang Zhou,&nbsp;Jie Zhang","doi":"10.1155/ijog/2729004","DOIUrl":"10.1155/ijog/2729004","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) ranks among the world′s most lethal cancers, with the majority of cases diagnosed at advanced stages. Accurate prognostic assessment is therefore essential for HCC management. This study utilized DNA methylation (MDGs) and RNA-sequencing data to develop and validate a predictive model for HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MDG profiles, RNA-seq data, and related clinical information were analyzed. Based on the Cancer Genome Atlas (TCGA) dataset, a prognostic signature was developed via univariable and multivariable Cox regression analyses in combination with LASSO regression. Subsequently, a nomogram model was constructed and calibrated using calibration curves. The predictive accuracy of the selected genes was tested through in vitro cellular experiments. In addition, the GDSC dataset was utilized to examine the association between the prognostic signature and drug resistance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Three genes (GLS, TEAD4, and CLGN) were identified and incorporated into the prognostic signature. Low-risk patients exhibited notably improved overall survival (OS) in comparison to high-risk patients. A nomogram model was developed based on clinical variables associated with OS, and its predictive accuracy for OS in individuals with HCC was evaluated via calibration curves. In vitro experiments revealed that the proliferative capacity of cells was notably reduced in the knockout group. The GDSC database was utilized to examine the association between the identified prognostic features and drug resistance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Predictive risk scores were developed based on three candidate MDGs, and a nomogram model was built by integrating clinical variables with these scores. This model can provide personalized prognosis prediction and assess drug resistance among individuals with HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12838239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093090","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":"Antimicrobial Resistant Factors in Klebsiella pneumoniae Strains Isolated From Urinary Tract Infections, Wound Infections, Hospital Wastewater, and Cervical Cancers From Ghana, Togo, and Benin","authors":"Biigba Yakubu","doi":"10.1155/ijog/5079377","DOIUrl":"10.1155/ijog/5079377","url":null,"abstract":"<p><i>Klebsiella pneumoniae</i> is a Gram-negative, facultatively anaerobic member of the Enterobacteriaceae that functions both as a gut commensal and a major opportunistic pathogen implicated in severe hospital and community-acquired infections. The rapid global expansion of antimicrobial-resistant <i>K. pneumoniae</i> lineages, particularly ESBL- and carbapenemase-producing strains, poses an escalating public health threat by eroding available treatment options. This study investigated the genomic architecture and resistance mechanisms of <i>K. pneumoniae</i> isolates recovered from urinary tract infections, wound infections, and cervical cancer cases across Ghana, Togo, and Benin. Eight isolates were subjected to antimicrobial susceptibility profiling and whole genome sequencing using the Illumina MiSeq platform after DNA extraction via the Zymo protocol. Comprehensive genomic analyses including MLST, resistance gene detection (Abricate), phylogenetic reconstruction (iTOL), genomic island prediction (IslandViewer), genome structural analysis (Proksee), and statistical interrogation in R (v4.4.0) were performed to characterize genetic diversity and identify determinants of antimicrobial resistance. The isolates exhibited heterogeneous but overlapping resistance profiles, extensive carriage of AMR genes, and the presence of multiple genomic islands enriched for integrases, transposases, and antibiotic resistance cassettes. MLST and SNP-based comparisons revealed both clonal clusters and genetically divergent lineages, while recombination analysis indicated mutation-driven evolution with lineage-specific recombination hotspots. Conserved gene orientation patterns and regions of atypical GC content further suggested historical acquisition of mobile genetic elements, including plasmid integrations and resistance islands. Collectively, these findings demonstrate the high genomic plasticity, multidrug-resistant phenotypes, and dynamic evolutionary processes shaping <i>K. pneumoniae</i> populations circulating in West Africa. The study underscores the urgent need for continuous regional genomic surveillance to guide treatment policies and limit the further dissemination of high-risk AMR clones.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051889","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 Multiomics Nominate GGCT as a Crucial Regulator of Immunosuppression in Colorectal Cancer","authors":"Qichao Niu,&nbsp;Yang Liu,&nbsp;Kejin Huang,&nbsp;Lisheng Nie,&nbsp;Shiming Zhao,&nbsp;Shifeng Yang,&nbsp;Changlei Su","doi":"10.1155/ijog/7013449","DOIUrl":"10.1155/ijog/7013449","url":null,"abstract":"<p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with tumor microenvironment (TME) heterogeneity playing a critical role in disease progression and therapeutic response. Immune escape (IE) mechanisms facilitate tumor evasion from host immune surveillance, yet their characterization at the single-cell level in CRC is incomplete. This study integrated single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic data from multiple public cohorts to systematically explore IE-related signatures in CRC. We identified major and minor cell populations within the TME and performed differential gene expression analysis. Using high-dimensional weighted gene coexpression network analysis (hdWGCNA), we identified gene modules correlated with IE activity. Subsequent survival analysis across six independent cohorts revealed Gamma-glutamylcyclotransferase (GGCT) as a novel prognostic biomarker associated with poor survival. Functional enrichment analysis indicated GGCT′s involvement in critical oncogenic pathways. Furthermore, GGCT expression correlated with altered immune infiltration profiles and stromal components, suggesting its role in modulating the immunosuppressive TME. Additionally, GGCT demonstrated potential predictive value for response to immunotherapy across multiple datasets. Our findings highlight GGCT as a key player in CRC immune evasion and a promising therapeutic target.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029728","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":"Mechanism of Non–Small Cell Lung Cancer–Derived Extracellular Vesicle miRNA hsa-let-7b-5p Targeting AP1S1 to Regulate M2 Macrophage Polarization","authors":"Lijuan Liu,&nbsp;Zixing Kou,&nbsp;Tianhua Wang,&nbsp;Qihang Shang,&nbsp;Qinxiang Zhang,&nbsp;Guanghui Liu,&nbsp;Jing Ai,&nbsp;Yanwen Zhao,&nbsp;Changgang Sun","doi":"10.1155/ijog/8220478","DOIUrl":"10.1155/ijog/8220478","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Non–small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. Further, the complex tumor immune microenvironment (TIME) is a critical factor in treatment resistance and poor prognosis associated with tumors. Tumor-associated macrophages (TAMs), a major component of the TIME, significantly promote tumor progression through their polarization toward the immunosuppressive M2 phenotype. Reportedly, NSCLC cells regulate TAM polarization by secreting extracellular vesicles (EVs) to deliver miRNAs; however, the specific underlying molecular mechanisms remain unclear. In this study, we aimed to elucidate the regulatory role of miRNAs derived from NSCLC EVs in TAM polarization and explore potential novel therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Through high-throughput sequencing and bioinformatics analysis, key regulatory targets were screened. Ki-67 staining was employed to detect cell proliferation, flow cytometry was performed to analyze cell apoptosis, RT-qPCR and Western blot were used to measure mRNA and protein expression levels, and Transwell assays were conducted to assess cell migration and invasion capabilities to investigate the molecular mechanisms underlying the miRNA-mediated regulation of TAM polarization by NSCLC-derived EVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NSCLC-derived EVs were successfully isolated and characterized. Bioinformatics analysis of EVs′ miRNA sequencing data revealed that the hsa-let-7b-5p/Adaptor-Related Protein Complex 1 subunit sigma 1 (AP1S1) axis may be a key regulator of TAM polarization. In vitro experiments confirmed that the hsa-let-7b-5p mimic potentially suppressed M2 polarization of TAMs via the AP1S1/p53 signaling axis, thereby attenuating the proliferation, migration, and invasion capabilities of NSCLC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study revealed the molecular mechanism by which hsa-let-7b-5p reshapes the immune microenvironment of NSCLC cells by targeting and inhibiting AP1S1 expression, thereby regulating the polarization of TAMs toward the M2 phenotype. Thus, the hsa-let-7b-5p/AP1S1 axis may serve as a potential therapeutic target for NSCLC immunotherapy, providing novel strategies for improving patient prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997772","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 Bioinformatics and Machine Learning Identify Novel Diagnostic Biomarkers and Molecular Mechanisms in Sjögren’s Syndrome","authors":"Hua Xu,&nbsp;Yong Liu,&nbsp;Yuyin Song,&nbsp;Yifan Zheng,&nbsp;Haifeng Jing,&nbsp;Yanfei Gao,&nbsp;Depeng Zhou,&nbsp;Xiang Chi,&nbsp;Jia Chen","doi":"10.1155/ijog/5044551","DOIUrl":"10.1155/ijog/5044551","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;Sjögren’s syndrome (SS) is a chronic autoimmune disorder characterized by significant diagnostic challenges due to nonspecific symptoms and a lack of reliable biomarkers, often resulting in delayed diagnosis and suboptimal patient management.&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;This study is aimed at identifying novel diagnostic biomarkers and elucidating the molecular mechanisms underlying SS pathogenesis through integrative bioinformatics and machine learning approaches.&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 analyzed three peripheral blood transcriptomic datasets (GSE51092, GSE66795, and GSE84844) comprising a total of 351 SS patients and 91 healthy controls. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and 12 machine learning algorithms were employed to identify robust diagnostic biomarkers. Immune cell infiltration was assessed using CIBERSORT, and single-cell RNA sequencing data (GSE157278) were analyzed to validate cell-type-specific expression patterns. Drug repurposing analysis was conducted using the L1000FWD platform.&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 identified 12 hub genes (EPSTI1, IFIH1, CXCL10, TNFSF10, GBP5, PARP9, IFI44, LAP3, IFIT2, IFI44L, PARP12, and OAS1) with exceptional diagnostic performance (AUC = 0.994 in training, 0.838 in internal validation, and 0.825 in external validation). These biomarkers showed significant correlations with clinical indicators including ANA, Ro/SSA, and La/SSB (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Immune-infiltration analysis revealed pronounced immune dysregulation in SS patients, characterized by an imbalance between naive and memory B cells and reduced CD8&lt;sup&gt;+&lt;/sup&gt; T cells and regulatory T cells (Tregs). Single-cell transcriptomics confirmed predominant expression in monocytes and dendritic cells, with additional significant expression in B cells and CD4&lt;sup&gt;+&lt;/sup&gt; T cells. Virtual knockdown analysis implicated these genes in antigen presentation, interferon signaling, and leukocyte trafficking. Drug repurposing identified FDA-approved candidates such as nisoldipine and exemestane as potential therapeutics.&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;Our integrative approach identifies 12 robust diagnostic biomarkers for SS, offering new insights into disease mechanisms and highlighting potential therapeutic targets for this challenging autoimmune disorder.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998090","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":"Pancancer Analyses of KISS1 as a Potential Biomarker for Tumor Metastasis and Immunotherapy and Therapeutic Target for Breast Cancer","authors":"Chunbiao Wu,&nbsp;Hao Jiang,&nbsp;Wei Xu,&nbsp;Bo Li,&nbsp;Hao Zhang,&nbsp;Long Zhang,&nbsp;Zhenxi Li,&nbsp;Jianru Xiao","doi":"10.1155/ijog/5902518","DOIUrl":"10.1155/ijog/5902518","url":null,"abstract":"<p>Emerging evidence highlights the pivotal role of KISS1 in cancer metastasis; however, there remains a dearth of pancancer analyses, particularly concerning immunotherapy. Here, we conducted a comprehensive investigation of KISS1 across various cancers, with a specific focus on breast cancer, using TCGA and GTEx datasets. We observed a tissue context-dependent role function of KISS1 in tumor metastasis, which exhibited suppressive effects in various tumors but promoted the metastatic phenotype in breast cancer. Our study revealed a noteworthy disparity between KISS1 expression at the mRNA and protein levels, indicating potential posttranslational modifications within cancer cells. Moreover, KISS1 is significantly associated with immune cell infiltration and immunosuppressive cells, suggesting its crucial role in modulating tumor immunotherapy. Intriguingly, our investigation also elucidated KISS1’s involvement in promoting breast cancer metastasis, thereby providing valuable insights into the molecular underpinnings of this process. Furthermore, we validated the presence of posttranslational modifications of KISS1 in breast cancer, adding to our understanding of its role in tumorigenesis. By shedding light on the tissue context-dependent function of KISS1 and its implications for immunotherapy, our pancancer study offers novel perspectives on the oncogenic roles of KISS1 and provides potential avenues for the development of targeted therapies and diagnostic biomarkers.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12780545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951888","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 Two Rare Variants in Iranian Families With Familial Sudden Cardiac Death","authors":"Mahsa Tahmasebivand,&nbsp;Sepideh Mehvari,&nbsp;Fatemeh Ghodratpour,&nbsp;Hamidreza Khoram Khorshid,&nbsp;Reza Malekzadeh,&nbsp;Reza Najafipour,&nbsp;Yasser Riazalhosseini,&nbsp;Mark Lathrop,&nbsp;Hossein Najmabadi,&nbsp;Kimia Kahrizi","doi":"10.1155/ijog/5965922","DOIUrl":"10.1155/ijog/5965922","url":null,"abstract":"<p>Cellular action potential is characterized by a particular sequence of depolarizing and repolarizing ion currents regulated by ion channels. Genetic mutations in these channels disrupt the essential movement of ions, such as Na+, Ca++, and K+, across the cell membrane, leading to dangerous arrhythmias and sudden cardiac death (SCD). Most cases of unexplained SCD are caused by pathogenic variants in genes linked to channelopathies and cardiomyopathy. Genetic investigations might aid in confirming the clinical diagnosis based solely on observations. Other advantages of genetic studies are clinical management of the patient, family screening, appropriate genetic counseling, and risk assessment for family members. This study was conducted to investigate the genetic cause of early-onset SCD in two Iranian families. Whole-exome sequencing was performed on the probands from each family, and the Illumina DRAGEN haplotype variant calling system was used to identify variants in each patient. Here, we identified rare heterozygous missense variants in the <i>RYR2</i> and <i>SCN5A</i> genes, which are linked to cardiac channelopathies. Alignment studies reveal that the mutated residues are conserved across humans and primates, underscoring their crucial role in protein function. Previously reported associations between these mutations and channelopathy pathogenesis have been confirmed in the present study. This study provides valuable insights for genetic counseling of families with a history of sudden death.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12776007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933146","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":"Single-Cell RNA-seq Reveals Deubiquitination Genes as Prognostic Markers in Hepatocellular Carcinoma","authors":"Xuening Lv,&nbsp;Chaozhou Chen,&nbsp;Shuxian Zhang,&nbsp;Feng Liang,&nbsp;Qing Zhang","doi":"10.1155/ijog/4893924","DOIUrl":"10.1155/ijog/4893924","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) carries a dismal prognosis, yet the contribution of deubiquitination—an essential posttranslational regulator—to its progression remains poorly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell RNA-seq profiles of 13 treatment-naïve HCC tumors were integrated with 374 TCGA and 243 ICGC bulk RNA-seq cohorts. Deubiquitinase (DUB) activity was quantified per cell with AUCell; pathway enrichment was performed with clusterProfiler. A LASSO-Cox machine learning pipeline was used to build a DUB-based risk signature, which was cross-validated internally and externally by time-dependent ROC analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Malignant cells exhibited divergent DUB transcription relative to immune compartments (myeloid, B). DUB-high neoplastic subsets displayed heightened inflammatory and IFN-<i>γ</i> signaling, concordant with brisk immune infiltration. A 78-gene prognostic index robustly stratified survival in discovery and replication cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study highlights the role of deubiquitination in HCC progression and its potential as a prognostic biomarker. The developed model could serve as a valuable tool for patient stratification and personalized treatment strategies, although further experimental validation is needed to confirm these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2026 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951837","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}