Comparative and Functional Genomics最新文献

{"title":"Establishing a Prognostic Model Correlates to Inflammatory Response Pathways for Prostate Cancer via Multiomic Analysis of Lactylation-Related Genes","authors":"Qinglong Du,&nbsp;CuiYu Meng,&nbsp;Wenchao Zhang,&nbsp;Li Huang,&nbsp;Chunlei Xue","doi":"10.1155/ijog/6681711","DOIUrl":"https://doi.org/10.1155/ijog/6681711","url":null,"abstract":"<p>Prostate cancer (PCa) continues to pose substantial clinical challenges, with molecular heterogeneity significantly impacting therapeutic decision-making and disease trajectories. Emerging evidence implicates protein lactylation—a novel epigenetic regulatory mechanism—in oncogenic processes, though its prognostic relevance in PCa remains underexplored. Through integrative bioinformatics interrogation of lactylation-associated molecular signatures, we established prognostic correlations using multivariable feature selection methodologies. Initial screening via differential expression analysis (limma package) coupled with Cox proportional hazards modeling revealed 11 survival-favorable regulators and 16 hazard-associated elements significantly linked to biochemical recurrence. To enhance predictive precision, ensemble machine learning frameworks were implemented, culminating in a 10-gene lactylation signature demonstrating robust discriminative capacity (concordance index = 0.738) across both primary (TCGA-PRAD) and external validation cohorts (DKFZ). Multivariable regression confirmed the lactylation score’s prognostic independence, exhibiting prominent associations with clinicopathological parameters including tumor staging and metastatic potential. The developed clinical-molecular nomogram achieved superior predictive accuracy (C − index &gt; 0.7) through the synergistic integration of biological and clinical covariates. Tumor microenvironment deconvolution uncovered distinct immunological landscapes, with high-risk stratification correlating with enriched stromal infiltration and immunosuppressive phenotypes. Pathway enrichment analyses implicated chromatin remodeling processes and cytokine-mediated inflammatory cascades as potential mechanistic drivers of prognostic divergence. Therapeutic vulnerability profiling demonstrated differential response patterns: low-risk patients exhibited enhanced immune checkpoint inhibitor responsiveness, whereas high-risk subgroups showed selective chemosensitivity to docetaxel and mitoxantrone. Functional validation in PC-3 models revealed AK5 silencing induced proapoptotic effects, suppressed metastatic potential of migration and invasion, and modulated immune checkpoint regulation through CD276 coexpression. These multimodal findings position lactylation dynamics, particularly AK5-mediated pathways, as promising therapeutic targets and stratification biomarkers in PCa management.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/6681711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689347","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":"Unraveling the PANoptosis Landscape in Osteosarcoma: A Single-Cell Sequencing and Machine Learning Approach to Prognostic Modeling and Tumor Microenvironment Analysis","authors":"Xue-yang Gui,&nbsp;Jun-fei Wang,&nbsp;Yi Zhang,&nbsp;Zi-yang Tang,&nbsp;Ze-zhang Zhu","doi":"10.1155/ijog/6915258","DOIUrl":"https://doi.org/10.1155/ijog/6915258","url":null,"abstract":"<p><b>Background:</b> Osteosarcoma (OS) is a highly aggressive bone malignancy prevalent in children and adolescents, characterized by poor prognosis and limited therapeutic options. The tumor microenvironment (TME) and cell death mechanisms such as PANoptosis—comprising pyroptosis, apoptosis, and necroptosis—play critical roles in tumor progression and immune evasion. This study is aimed at exploring the PANoptosis landscape in OS using single-cell RNA sequencing (scRNA-seq) and at developing a robust prognostic model using machine learning algorithms.</p><p><b>Methods:</b> Single-cell sequencing data for OS were obtained from the GEO database (GSE162454), and bulk transcriptome data were sourced from the TARGET and GEO databases. Data integration, dimensionality reduction, and cell clustering were performed using UMAP and t-SNE. PANoptosis-related genes were identified, and their expression profiles were used to score and categorize cells into PANoptosis-high and PANoptosis-low groups. A comprehensive prognostic model was constructed using 101 machine learning algorithms, including CoxBoost, to predict patient outcomes. The model’s performance was validated across multiple cohorts, and its association with the mutation landscape and TME was evaluated.</p><p><b>Results:</b> The scRNA-seq analysis revealed 14 distinct cell clusters within OS, with significant PANoptosis activation observed in cancer-associated fibroblasts (CAFs), myeloid cells, osteoblasts, and osteoclasts. Differentially expressed genes between PANoptosis-high and PANoptosis-low groups were identified, and cell communication analysis showed enhanced interaction patterns in the PANoptosis-high group. The CoxBoost model, selected from 101 machine learning algorithms, exhibited stable prognostic performance across the TARGET and GEO cohorts, effectively stratifying patients into high-risk and low-risk groups. The high-risk group displayed worse survival outcomes, higher mutation frequencies, and distinct immune infiltration patterns, correlating with poorer prognosis and increased tumor purity.</p><p><b>Conclusion:</b> This study provides novel insights into the PANoptosis landscape in OS and presents a validated prognostic model for risk stratification. The integration of scRNA-seq data with machine learning approaches enhances our understanding of OS heterogeneity and its impact on patient prognosis, offering potential avenues for targeted therapeutic strategies. Further validation in clinical settings is warranted to confirm the model’s utility in guiding personalized treatment for OS patients.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/6915258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689084","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":"SMPD3 as a Potential Biomarker and Therapeutic Target in Hepatocellular Carcinoma","authors":"Dan Zhu,&nbsp;Lei Cao","doi":"10.1155/ijog/5443244","DOIUrl":"https://doi.org/10.1155/ijog/5443244","url":null,"abstract":"<p><b>Background and Aims:</b> Hepatocellular carcinoma (HCC) is a prevalent and aggressive liver cancer with high mortality rates. Sphingomyelin phosphodiesterase 3 (SMPD3) has recently been suggested to play an antitumor role in several cancers. This study is aimed at investigating the role of SMPD3 in HCC and its potential as a prognostic marker and therapeutic target.</p><p><b>Methods:</b> A retrospective cohort study of HCC patients was conducted using clinical data from our hospital. Survival analyses, including Kaplan–Meier and multivariate Cox regression, were performed to assess the impact of SMPD3 expression on survival. Further analyses were carried out using data from The Cancer Genome Atlas (TCGA) HCC cohort. In vitro and in vivo experiments were conducted to evaluate the effects of SMPD3 overexpression on HCC cell lines and tumor growth in mice.</p><p><b>Results:</b> High SMPD3 expression level was associated with improved survival in both our cohort and TCGA cohort. Multivariate Cox regression analysis confirmed high SMPD3 expression level as an independent predictor of better survival outcomes. In vitro and in vivo experiments demonstrated that SMPD3 overexpression significantly decreased HCC cell proliferation, migration, and invasion and inhibited tumor growth in a nude mouse model.</p><p><b>Conclusions:</b> SMPD3 plays a protective role in HCC by inhibiting tumor growth and progression. Its high expression is associated with better survival outcomes and may serve as a promising prognostic marker and potential therapeutic target in HCC. Further research into the molecular mechanisms of SMPD3’s antitumor effects could lead to novel therapeutic strategies for HCC.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/5443244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594937","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":"Construction and Validation of a T Cell Exhaustion–Related Prognostic Signature in Cholangiocarcinoma","authors":"Changshi Qian,&nbsp;Yuqiao Sun,&nbsp;Yihuai Yue","doi":"10.1155/ijog/8823837","DOIUrl":"https://doi.org/10.1155/ijog/8823837","url":null,"abstract":"<p><b>Objective:</b> T cell exhaustion (TEX) is a critical determinant of immune resistance. This study was performed to investigate the key genes linked to TEX in cholangiocarcinoma (CCA) and construct a TEX-associated gene signature to forecast the prognosis of patients with CCA.</p><p><b>Methods:</b> Based on the expression data acquired from the E-MTAB-6389 dataset, the TEX-related modules and module genes were identified using weighted coexpression network analysis (WGCNA). Subsequently, a TEX-related prognostic signature was built by using the univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. The immune cell infiltration in each CCA sample was evaluated using the single-sample gene set enrichment analysis (ssGSEA) package, followed by single-cell RNA sequencing (scRNA-seq) analysis. Furthermore, the expression of TEX-related genes in the gene signature was experimentally validated in CCA cells by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot analysis.</p><p><b>Results:</b> A total of 15 TEX-associated modules and 23 module genes were identified. Then, a four-gene signature related to TEX was established, containing Palladin, Cytoskeletal Associated Protein (<i>PALLD</i>), Member RAS Oncogene Family (<i>RAB31</i>), ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (<i>ADAMTS2</i>), and <i>WISP1</i>, which could predict prognosis of patients with CCA. Moreover, neutrophils, endothelial cells, B cells, and T cells exhibited significant infiltration in CCA samples, and these four TEX-related genes were both significantly positively correlated with T cells, endothelial cells, and B cells while negatively correlated with neutrophils. Moreover, a total of 13 cell types were annotated after scRNA-seq analysis. Notably, <i>RAB31</i> was mainly highly expressed in monocytes, macrophages, DC2 (Dendritic Cells 2), and DC3 (Dendritic Cells 3), and <i>PALLD</i>, <i>ADAMTS2</i>, and <i>WISP1</i> were mainly overexpressed in fibroblasts. Furthermore, experimental validation revealed that the expression levels of <i>PALLD</i>, <i>RAB31</i>, <i>ADAMTS2</i>, and <i>WISP1</i> were consistent with the trend results of bioinformatics analysis.</p><p><b>Conclusion:</b> A prognostic signature was developed by four TEX-related genes, including <i>PALLD</i>, <i>RAB31</i>, <i>ADAMTS2</i>, and <i>WISP1</i>, which might be a powerful predictor for the prognosis of patients with CCA. These TEX-related genes were related to the infiltration of neutrophils, endothelial cells, B cells, and T cells in CCA.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/8823837","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581934","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":"Analysis of Gene Regulatory Networks of Taro (Colocasia esculenta (L.) Schott.) Soluble Starch Synthase Based on DeGN and KASP Marker Development","authors":"Lu Jiang,&nbsp;Jianmei Yin,&nbsp;Li Wang,&nbsp;Xiaoyong Han,&nbsp;Peitong Zhang","doi":"10.1155/ijog/9953367","DOIUrl":"https://doi.org/10.1155/ijog/9953367","url":null,"abstract":"<p>Taro (<i>Colocasia esculenta</i> (L.) Schott.) is an important edible and economically valuable crop that is also a source of high-quality starch. Its quality is determined by the content and proportion of amylopectin. Based on transcriptome sequencing of corms at different growth stages (T1–T6), 34,603 transcripts and 1727 novel genes with functional annotation were obtained. In total, 11,865 differentially expressed genes (DEGs) were identified among six development stages, with 3836 and 3404 DEGs in T2 versus T3 and T3 versus T4, respectively. The regulatory network of taro starch synthesis was constructed on the DeGNServer. Among three cloned soluble starch synthase (SS) genes, <i>CeSS II</i> might be the key gene responsible for soluble starch synthesis in taro corm. The putative transcription factor <i>CeMyb108</i> might play a negative role in starch synthesis. Sanger sequencing <i>CeSS II</i> gene revealed a single nucleotide polymorphism (SNP) between two variety groups with high and low starch content. A kompetitive allele-specific PCR (KASP) marker, namely, CeSS II-SNP, was developed and validated in a natural population of 89 taro accessions. The starch content of the C:T group amounts to 517.45 mg/g, which is significantly (22.3%) higher than its counterpart (T:T). This newly developed marker is proved to be effective and would facilitate marker-assisted breeding for taro with high starch content.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/9953367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521929","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":"Frequency of Genetic Testing Among Patients With Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancers: A Strategy to Improve Compliance","authors":"Jude Nawlo,&nbsp;Kevin Espino,&nbsp;Deanna Gerber,&nbsp;Meredith Akerman,&nbsp;Kent Chan,&nbsp;Edward Jimenez,&nbsp;Eva Chalas","doi":"10.1155/ijog/9281891","DOIUrl":"https://doi.org/10.1155/ijog/9281891","url":null,"abstract":"<p><b>Purpose:</b> In 2014, the Society of Gynecologic Oncology (SGO) recommended universal germline testing for all patients with epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or peritoneal cancer (PC). Despite this position statement, genetic testing (GT) uptake among affected patients remains well below the universal testing goal. The aim of this study is to evaluate the impact of an internal policy change on the GT rate at a single institution.</p><p><b>Patients and Methods:</b> This investigation was an Institutional Review Board (IRB)–approved (#22-00711) retrospective cohort study which took place at a single institution from June 2021 to April 2022. The study assessed GT uptake among patients diagnosed with EOC, FTC, and PC to evaluate the following internal policy change integrating point-of-care (POC) GT.</p><p><b>Results:</b> A total of 272 patients were identified with 47 patients excluded due to nonepithelial tumors. Genetic counseling was documented in 94.2% of eligible patients (212/225) and completed in 90.2% (203/225). Of the 22 (9.8%) who were not genetically tested, 27% (6/22) were offered and declined. Deleterious mutations were identified in 22% (45/205) of patients tested. Of these, 82.2% (37/45) were in BRCA, 6.8% (3/45) in Lynch-associated mutations (MSH2, MSH6, MLH1, and PMS2), 4.4% (2/45) in RAD51, 4.4% (2/45) in BRIP1, and 2.2% (1/45) in an unknown deleterious mutation reportedly diagnosed at a different facility.</p><p><b>Conclusion:</b> Internal policy developed based on analysis of compliance with the SGO position statement and subsequent implementation of POC testing led to a significant increase in GT, indicating improvement in quality medical care. GT rates in this population are markedly higher than reported in the literature.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/9281891","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521931","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":"Correlation Analysis of Pyroptosis-Related Genes CASP1, NLRP3, AIM2, and NLRP1 With Lung Adenocarcinoma","authors":"Lingling Zhu,&nbsp;Yongqian Zhang,&nbsp;Xiaojing Chen,&nbsp;Yuehang Li,&nbsp;Haiqiao Pan,&nbsp;Yuan Wang,&nbsp;Ning Chen,&nbsp;Yajing Wu,&nbsp;Yishuai Li,&nbsp;Min Zhao","doi":"10.1155/ijog/8282590","DOIUrl":"https://doi.org/10.1155/ijog/8282590","url":null,"abstract":"<p><b>Purpose:</b> This study is aimed at exploring the role of pyroptosis-related genes in the development, immune infiltration, and clinical features of lung adenocarcinoma.</p><p><b>Method:</b> Pyroptosis-related genes were searched using online databases, including MSigDB, Gene, and GeneCards. We explored pyroptosis-related gene expression patterns in lung adenocarcinoma using the UALCAN database. Functional enrichment analysis of pyroptosis-related genes in lung adenocarcinoma was performed using the Metascape database. A protein–protein interaction network was constructed using the STRING database, and the outcomes were visualized using Cytoscape. The top five core genes were screened utilizing the MCC algorithm with its cytoHubba plugin. The correlation between immune cell infiltration, diagnosis, and prognosis of core genes in lung adenocarcinoma was explored using the TIMER 2.0, TCGA, and Kaplan–Meier plotter databases. A nomogram was constructed to predict the survival of patients with lung adenocarcinoma using Cox regression analysis, and its clinical value was validated. Samples of paraffin-embedded lung adenocarcinoma tissues were collected and subjected to immunohistochemical tests to verify the expression of core genes in lung adenocarcinoma and adjacent tissues.</p><p><b>Results:</b> Overall, 202 genes related to pyroptosis were identified, with 67 upregulated and 60 downregulated in lung adenocarcinomas. The top five core genes—namely, CASP1 (caspase1), PYCARD (PYD and CARD domain-containing protein), NLRP3 (NOD-like receptor protein 3), AIM2 (absent in melanoma 2), and NLRP1 (NOD-like receptor protein 1)—related to lung adenocarcinoma pyroptosis were selected. The correlation analysis of immune cell infiltration showed that CASP1, NLRP3, and AIM2, which showed that pyroptosis was involved in the infiltration of immune cells in the tumor microenvironment and NLRP1 exhibited high diagnostic efficacy, while PYCARD demonstrated poor diagnostic efficacy. High expression of CASP1, NLRP3, and NLRP1 correlated with a better prognosis (<i>p</i> &lt; 0.05), while elevated AIM2 expression was associated with a poor prognosis (<i>p</i> &lt; 0.05). However, PYCARD exhibited no significant correlation with prognosis (<i>p</i> &gt; 0.05). The immunohistochemistry results showed that positive rates of CASP1, NLRP3, AIM2, and NLRP1 were 20%, 15%, 70%, and 10%, respectively, while in adjacent tissues, the positive rates were 60%, 60%, 20%, and70%, indicating high expression of AIM2 and low expression of CASP1, NLRP3, and NLRP1 in lung adenocarcinoma.</p><p><b>Conclusion:</b> CASP1, NLRP3, AIM2, and NLRP1 are core pyroptotic genes in lung adenocarcinoma and exhibit a strong correlation with immune cell infiltration, diagnosis, and prognosis of this condition. These genes may be useful in the clinical diagnosis and treatment of patients with lung adenocarcinoma.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/8282590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466070","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":"PANoptosis-Related Optimal Model (PROM): A Novel Prognostic Tool Unveiling Immune Dynamics in Lung Adenocarcinoma","authors":"Jianming Peng,&nbsp;Leijie Tong,&nbsp;Rui Liang,&nbsp;Huisen Yan,&nbsp;Xiuling Jiang,&nbsp;Youai Dai","doi":"10.1155/ijog/5595391","DOIUrl":"https://doi.org/10.1155/ijog/5595391","url":null,"abstract":"<p><b>Background:</b> PANoptosis, a recently characterized inflammatory programmed cell death modality orchestrated by the PANoptosome complex, integrates molecular mechanisms of pyroptosis, apoptosis, and necroptosis. Although this pathway potentially mediates tumor progression, its role in lung adenocarcinoma (LUAD) remains largely unexplored.</p><p><b>Methods:</b> Through comprehensive single-cell transcriptomic profiling, we systematically identified critical PANoptosis-associated gene signatures. Prognostic molecular determinants were subsequently delineated via univariate Cox proportional hazards regression analysis. We constructed a PANoptosis-related optimal model (PROM) through the integration of 10 machine learning algorithms. The model was initially developed using The Cancer Genome Atlas (TCGA)-LUAD cohort and subsequently validated across six independent LUAD cohorts. Model performance was evaluated using mean concordance index. Furthermore, we conducted extensive multiomics analyses to delineate differential pathway activation patterns and immune cell infiltration profiles between PROM-stratified risk subgroups.</p><p><b>Results:</b> Cellular populations exhibiting elevated PANoptosis signatures demonstrated enhanced intercellular signaling networks. PROM demonstrated superior prognostic capability across multiple validation cohorts. Receiver operating characteristic curve analyses revealed area under the curve values exceeding 0.7 across all seven cohorts, with several achieving values above 0.8, indicating robust discriminative performance. The model score exhibited significant correlation with immunological parameters. Notably, high PROM scores were associated with attenuated immune responses, suggesting an immunosuppressive tumor microenvironment. Multiomics investigations revealed significant alterations in critical oncogenic pathways and immune landscape between PROM-stratified subgroups.</p><p><b>Conclusion:</b> This investigation establishes PROM as a clinically applicable prognostic tool for LUAD risk stratification. Beyond its predictive utility, PROM elucidates PANoptosis-associated immunological and biological mechanisms underlying LUAD progression. These findings provide novel mechanistic insights into LUAD pathogenesis and may inform the development of targeted therapeutic interventions and personalized treatment strategies to optimize patient outcomes.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/5595391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431603","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":"Establishment of a Lactylation-Related Gene Signature for Hepatocellular Carcinoma Applying Bulk and Single-Cell RNA Sequencing Analysis","authors":"Lianghe Yu,&nbsp;Yan Shi,&nbsp;Zhenyu Zhi,&nbsp;Shuang Li,&nbsp;Wenlong Yu,&nbsp;Yongjie Zhang","doi":"10.1155/ijog/3547543","DOIUrl":"https://doi.org/10.1155/ijog/3547543","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Lactylation is closely involved in cancer progression, but its role in hepatocellular carcinoma (HCC) is unclear. The present work set out to develop a lactylation-related gene (LRG) signature for HCC.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The lactylation score of tumor and normal groups was calculated using the gene set variation analysis (GSVA) package. The single-cell RNA sequencing (scRNA-seq) analysis of HCC was performed in the “Seurat” package. Prognostic LRGs were selected by performing univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses to develop and validate a Riskscore model. Functional enrichment analysis was conducted by gene set enrichment analysis (GSEA) using the “clusterProfiler” package. Genomic characteristics between different risk groups were compared, and tumor mutational burden (TMB) was calculated by the “Maftools” package. Immune cell infiltration was assessed by algorithms of cell-type identification by estimating relative subsets of RNA transcript (CIBERSORT), microenvironment cell populations-counter (MCP-counter), estimating the proportions of immune and cancer cells (EPIC), tumor immune estimation resource (TIMER), and single-sample gene set enrichment analysis (ssGSEA). Immunotherapy response was predicted by the tumor immune dysfunction and exclusion (TIDE) algorithm. Drug sensitivity was analyzed using the “pRRophetic” package. A nomogram was established using the “rms” package. The expressions of the prognostic LRGs in HCC cells were verified by in vitro test, and cell counting kit-8 (CCK-8), wound healing, and transwell assays were carried out to measure the viability, migration, and invasion of HCC cells.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The lactylation score, which was higher in the tumor group than in the normal group, has been confirmed as an independent factor for the prognostic evaluation in HCC. Six prognostic LRGs, including two protective genes (&lt;i&gt;FTCD&lt;/i&gt; and &lt;i&gt;APCS&lt;/i&gt;) and four risk genes (&lt;i&gt;LGALS3&lt;/i&gt;, &lt;i&gt;C1orf43&lt;/i&gt;, &lt;i&gt;TALDO1&lt;/i&gt;, and &lt;i&gt;CCT5&lt;/i&gt;), were identified to develop a Riskscore model with a strong prognostic prediction performance in HCC. The scRNA-seq analysis revealed that &lt;i&gt;LGALS3&lt;/i&gt; was largely expressed in myeloid cells, while &lt;i&gt;APCS&lt;/i&gt;, &lt;i&gt;FTCD&lt;/i&gt;, &lt;i&gt;TALDO1&lt;/i&gt;, &lt;i&gt;CCT5&lt;/i&gt;, and &lt;i&gt;C1orf43&lt;/i&gt; were mainly expressed in hepatocytes. The high-risk group was primarily enriched in the pathways involved in tumor occurrence and development, with higher T cell infiltration. Moreover, the high-risk group was found to be less responsive to immunotherapy but was more sensitive to chemotherapeutic drugs. By integrating Riskscore and clinical features, a nomogram with a high predictive accuracy was developed. Additionally, &lt;i&gt;C1orf43&lt;/i&gt;, &lt;i&gt;CCT5&lt;/i&gt;, &lt;i&gt;TALDO1&lt;/i&gt;, and &lt;i&gt;LGALS3&lt;/i&gt; were highly expressed in HCC cells. Silencing &lt;i&gt;CCT5&lt;/i&gt; inhibited the viability, migration, and invasion of HCC cells.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; The present work deve","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/ijog/3547543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404407","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 Prognostic Riskscore Model Related to Helicobacter pylori Infection in Stomach Adenocarcinoma","authors":"Jing Peng,&nbsp;Qi Yan,&nbsp;Wennan Pei,&nbsp;Yi Jiang,&nbsp;Li Zhou,&nbsp;Ruoqing Li","doi":"10.1155/ijog/5554610","DOIUrl":"10.1155/ijog/5554610","url":null,"abstract":"<p><b>Background:</b> <i>Helicobacter pylori</i> (<i>HP</i>) is associated with the development of various stomach diseases, one of the major risk factors for stomach adenocarcinoma (STAD).</p><p><b>Methods:</b> The <i>HP</i> infection score between tumor and normal groups was compared by single-sample gene set enrichment analysis (ssGSEA). The key modules related to <i>HP</i> infection were identified by weighted gene coexpression network analysis (WGCNA), and functional enrichment analysis was conducted on these module genes. Further, the limma package was used to screen the differentially expressed genes (DEGs) between <i>HP</i>-positive and <i>HP</i>-negative STAD. The prognostic genes were obtained to construct the riskscore model, and the performance of the model was validated. The correlation between riskscore and tumor immune microenvironment (TIME) was analyzed by Spearman’s method. The single-cell atlas of <i>HP</i>-positive STAD was delineated. The mRNA expression levels of the prognostic genes were verified using STAD cells, and the migration and invasion capacities of STAD cells were evaluated by using the wound healing assay and transwell assay.</p><p><b>Results:</b> The <i>HP</i> infection score in the tumor group was significantly higher than that in the normal group. The purple and royal blue modules showed higher correlation with <i>HP</i> infection in STAD, and these module genes were enriched in the immune-related pathway. Further, five prognostic genes (<i>CTLA4</i>, <i>CPVL</i>, <i>EMB</i>, <i>CXCR4</i>, and <i>FAM241A</i>) were screened from the <i>HP</i> infection–related DEGs, which were utilized for establishing the riskscore model, with good robustness. Riskscore exhibited strong correlation with TIME in STAD. Single-cell atlas of <i>HP</i>-positive STAD revealed that <i>CXCR4</i> is highly expressed in Epithelial Cell 1, Epithelial Cell 2, and parietal cells of the tumor group. <i>CPVL</i>, <i>EMB</i>, <i>CTLA4</i>, <i>FAM241A</i>, and <i>CXCR4</i> showed high expression in STAD cells, and the silencing of <i>CPVL</i> could suppress the migration and invasion of STAD cells.</p><p><b>Conclusion:</b> This study established a riskscore model based on <i>HP</i> infection–related genes, which could provide reference for prognostic prediction and treatment targets of STAD.</p>","PeriodicalId":55239,"journal":{"name":"Comparative and Functional Genomics","volume":"2025 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065517","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}