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Identification of FZD7 as a potential ferroptosis-related diagnostic gene in endometriosis by bioinformatics analysis

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SCIENTIFIC REPORTS 2025年第1期15卷 1-10页

作者： Huang, Jianyun Li, Jinbo Li, Xiao Guo, Hongling Chen, Shuqin Sun Yat Sen Univ Affiliated Hosp 6 Dept Gynecol Guangzhou Peoples R China Sun Yat Sen Univ Affiliated Hosp 6 Biomed Innovat Ctr Guangzhou Peoples R China Sun Yat Sen Univ Affiliated Hosp 7 Dept Gynecol Shenzhen Peoples R China

An increasing number of research have suggested that ferroptosis plays an important role in endometriosis (EMS). This study was to identify a ferroptosis-related diagnosis gene in EMS by using bioinformatics. R Bioconductor package limma was used to analyzed the differentially expressed genes (DEGs) between the EMS groups and control groups. CIBERSORT was used to analyze the differences between the EMS group and control group of 22 immune cells. Quantitative real-time PCR (RT-qPCR) and Western blot (WB) were used to validate the expression level of FZD7 in tissue samples. The study found that FZD7 was upregulated and showed good diagnostic value in five EMS transcriptome databases. RT-qPCR and WB experiments also verified that FZD7 was upregulated in EMS. Moreover, we found that macrophages, especially M2 macrophages, were significantly infiltrated in EMS. FZD7 was positively correlated with M2 macrophage infiltration, and was up-regulated in the endometrial stromal cells co-cultured with macrophages. The study identified an ferroptosis repressor gene, FZD7, validated in five EMS transcriptome datasets, which is significantly up-regulated in ectopic lesions of EMS and is a potential target for the treatment of EMS.

关键词： Endometriosis Ferroptosis FZD7 bioinformatics analysis

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Identification of the potential role of S1PR1 in adult moyamoya disease based on multiple bioinformatics analysis and experimental verification

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FASEB JOURNAL 2025年第6期39卷 e70461页

作者： Zhou, Jiabin Lei, Yu Zhang, Shilin Qin, Renwu Liu, Yuhan Yi, Dongye Huazhong Univ Sci & Technol Union Hosp Tongji Med Coll Dept Neurosurg Wuhan 430022 Hubei Peoples R China Wuhan Univ Zhongnan Hosp Wuhan Peoples R China Naval Aviat Univ Chinese Peoples Liberat Army Yantai Peoples R China China Three Gorges Univ Peoples Hosp Yichang 3 Dept Endocrinol Peoples Hosp Yichang Peoples R China Hubei Prov Hosp Integrated Chinese & Western Med Dept Gastroenterol Wuhan 430024 Hubei Peoples R China

Moyamoya disease (MMD) is a chronic occlusive cerebrovascular ailment with a progressively rising incidence, yet its precise etiology and pathogenesis remain elusive. Adult MMD-related datasets GSE189993 and GSE157628 were procured from the GEO database for screening of differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was employed to unveil the most significant module associated with MMD. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to identify and validate diagnostic markers for MMD. CIBERSORT and ssGSEA analyses were conducted to estimate immune cell infiltration in MMD vessels. In vitro experiments were performed to validate the biological functions of Sphingosine-1-phosphate receptor 1 (S1PR1) in mouse aortic smooth muscle cells (MOVAS). A total of 436 DEGs were identified from GSE189993, comprising 202 up-regulated genes and 234 down-regulated genes. Within the green-yellow module, 87 genes overlapped with DEGs, and 6 genes were identified by Cytoscape as key factors in the pathophysiology of MMD, namely, platelet endothelial cell adhesion molecule 1 (PECAM1), von Willebrand factor (VWF), intercellular cell adhesion molecule 1 (ICAM1), vascular endothelial growth factor C (VEGFC), tissue-type plasminogen activator (PLAT), and S1PR1. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses also showed that key genes were mainly involved in endothelial cells and cell adhesion-related biological function. About 13 diagnostic genes were obtained by the LASSO regression algorithm, with S1PR1 emerging as a hub gene demonstrating good diagnostic performance in both the test set and validation set. Finally, we validated that overexpression of S1PR1 spurred viability, proliferation, and cell division in mouse aortic smooth muscle cells (MOVAS) and human cerebral vascular smooth muscle cells (HCVSMC) by activating the PI3K/AKT signaling pathway. S1PR1 has

关键词： bioinformatics analysis immune cell infiltration moyamoya disease S1PR1 WGCNA

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Pan-cancer bioinformatics analysis of TIPRL in human tumors

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DISCOVER ONCOLOGY 2025年第1期16卷 1-17页

作者： Zhang, Xuezhong Xue, Hao Lv, Yuanyuan Zhou, Yuntao Sha, Kaihui Liu, Tonggang Zibo Cent Hosp Dept Lab Med Zibo Shandong Peoples R China Zibo Cent Hosp Dept Neurol Zibo Shandong Peoples R China Zibo Cent Hosp Dept Cardiol Zibo Shandong Peoples R China Binzhou Med Univ Sch Nursing Binzhou Shandong Peoples R China Binzhou Med Univ Hosp Dept Infect Dis Binzhou Shandong Peoples R China

IntroductionThe TOR signaling pathway regulator-like (TIPRL) gene plays a multifaceted role in cancer, yet its pan-cancer profile remains underexplored. This study investigates TIPRL expression across multiple cancers and its associations with survival, genetic alterations, immune infiltration, and functional pathways, providing insights into TIPRL's role as a potential prognostic and therapeutic *** expression and prognostic significance across tumor types were analyzed using TCGA_GTEx and CPTAC data in R software and platforms like GEPIA2 and UALCAN. Genetic alterations and 3D structures were evaluated through cBioPortal. Associations with RNA modifications, immune checkpoints, immune cell infiltration, TMB, MSI, HRD, and enriched pathways were assessed via R and STRING databases, employing survival analysis, ssGSEA, and enrichment *** expression was elevated in most cancers, with significant stage-specific associations observed in KICH, KIRP, and LUSC. High TIPRL expression correlated with worse overall survival in ACC, BRCA, HNSC, KICH, LIHC, and MESO, suggesting its role in prognosis. Genetic analysis identified amplifications as the main alteration, with varied clinical relevance across cancers. RNA modifications in TIPRL, particularly m1A, m5C, and m6A, suggested potential regulatory mechanisms. Immune infiltration analysis revealed TIPRL's varied correlations with immune cell types and immune scores, differing by cancer type. TIPRL also positively correlated with TMB, MSI, and HRD in several cancers, indicating its association with genomic instability. Enrichment analyses highlighted TIPRL's involvement in processes like oxidative phosphorylation and autophagy, underscoring its influence in *** findings establish TIPRL as a significant biomarker in cancer progression and immune regulation, warranting further exploration into its therapeutic implications across diverse tumor types.

关键词： TOR signaling pathway regulator-like (TIPRL) gene Pan-cancer Tumor bioinformatics analysis

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Anti-cystitis glandularis action exerted by glycyrrhetinic acid: bioinformatics analysis and molecular validation

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MOLECULAR DIVERSITY 2025年 1-10页

作者： Hu, Haiwei Tang, Yongbo Zhou, Baotong Chen, Shuangyan Su, Jimin Zhong, Wei Wei, Yuanyang Huang, Yipeng Ge, Bo Guilin Med Univ Affiliated Hosp 2 Dept Urol Surg Guilin 541199 Guangxi Peoples R China Guilin Med Univ Guilin 541004 Peoples R China

Cystitis glandularis (CG) is a chronic hyperplastic disorder of the bladder, and the available clinical drug therapy is insufficient currently. Glycyrrhetinic acid (GA), a bioactive compound extracted from the roots of Glycyrrhiza glabra, is found with beneficial actions, including anti-inflammatory and anti-oxidative effects. We previously reported that GA relieves CG symptoms in animal model, implying the potential application of GA to treat CG. However, the action mechanisms of GA against CG remain unclear. In this study, we aimed to identify the pivotal targets and therapeutic effects of GA through integrated bioinformatics analysis and experimental validation. Integrated bioinformatics analysis screened eleven potential therapeutic targets for GA against CG, and seven pivotal targets were identified subsequently. Enrichment gene analysis revealed GA exhibiting biological activities against CG via regulating multiple pharmacological targets and molecular pathways associated with inflammatory reaction and oxidative stress. Molecular docking computation revealed potent affinity and interaction between GA and prostaglandin-endoperoxide synthase 2 (PTGS2) and mucin 1 (MUC1) proteins in CG. To validate biochemically, increased mRNA and protein expressions of PTGS2 and MUC1 were observed in human CG samples. Compared to CG mice, GA-treated CG mice exhibited reduced inflammatory cytokine contents and downregulated PTGS2 and MUC1 mRNA and protein levels. These integrated findings suggest the potential therapeutic effects of GA against CG via the regulation of targeting genes and pathways. However, further studies are necessary to perform and facilitate the clinical application of GA for treating CG.

关键词： bioinformatics analysis Glycyrrhetinic acid Cystitis glandularis Inflammation Oxidative stress Molecular validation

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A comprehensive investigation of identifying miRNA biomarkers and their potential role in age-related cataract by meta-analysis and bioinformatics analysis

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GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 2025年 1-19页

作者： Zhang, Kaiyun Chen, Li Qu, Laiqiang Yan, Hong Northwest Univ Shaanxi Eye Hosp Xian Peoples Hosp Xian Hosp 4 21 Jiefang Rd Xian 710004 Shaanxi Provinc Peoples R China

PurposeAge-related cataract (ARC) remains one of the leading causes of blindness globally. Despite the satisfactory outcomes of surgical interventions, significant disparities in access to medical care prevent many patients from receiving effective treatment. Thus, identifying reliable biomarkers and therapeutic targets to expand treatment options for ARC is essential. Recent evidence indicates that microRNAs (miRNAs) play a role in the development of cataracts and may serve as promising biomarkers. Consequently, this study aims to investigate miRNAs' levels and potential functions in *** conducted a meta-analysis following the PRISMA guidelines by searching three databases from inception to March 31, 2023. The quality of the articles was assessed using the NOS. Subsequently, the targets of the miRNAs identified in the meta-analysis were predicted using six databases, and their GO functions and KEGG pathway enrichment information were analyzed via *** initial search yielded 225 publications, from which 22 miRNAs across 37 studies were selected for our meta-analysis. We identified eight differentially expressed miRNAs (DEmiRNAs) in ARC, comprising two up-regulated miRNAs (miR-124 and miR-125a) and six down-regulated miRNAs (miR-15a, miR-23b, miR-34a, miR-221, miR-222, and miR-378a). A total of 972 targets for these miRNAs have been confirmed, and subsequent bioinformatics analysis has revealed their potential functions and pathways in various ARC-related *** study indicates that eight differentially expressed miRNAs (miRNA-15a, miRNA-23b, miRNA-34a, miRNA-124, miRNA-125a, miRNA-221, miRNA-222, and miRNA-378a) may serve as biomarkers for ARC. bioinformatics analyses suggest varied potential roles for each miRNA, providing a framework for future research in ARC. This systematic evaluation represents the initial depiction of the miRNA-biomarker landscape in *** MessagesWhat is knownMicroRNAs(miRNAs) could serve as biomarke

关键词： Age-related cataract MicroRNA Biomarker Meta-analysis bioinformatics analysis

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Identification of M1 macrophage infiltration-related genes for immunotherapy in Her2-positive breast cancer based on bioinformatics analysis and machine learning

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SCIENTIFIC REPORTS 2025年第1期15卷 1-18页

作者： Wang, Sizhang Wang, Xiaoyan Xia, Jing Mu, Qiang Qingdao Univ Qingdao Med Coll Qingdao 266042 Shandong Peoples R China Univ Hlth & Rehabil Sci Qingdao Cent Hosp Gen Practice Dept Qingdao 266042 Shandong Peoples R China Univ Hlth & Rehabil Sci Qingdao Cent Hosp Dept Breast Surg Qingdao 266042 Shandong Peoples R China

Over the past several decades, there has been a significant increase in the number of breast cancer patients. Among the four subtypes of breast cancer, Her2-positive breast cancer is one of the most aggressive breast cancers. In this study, we screened the differentially expressed genes from The Cancer Genome Atlas-Breast cancer database and analyzed the relationship between immune cell infiltration and differentially expressed genes using weighted gene co-expression network analysis. By constructing a module-trait relationships heatmap, the red module, which had the highest correlation value with M1 macrophages, was selected. Twenty hub genes were selected based on a protein-protein interaction network. Then, four overlapping M1 macrophage infiltration-related genes (M1 MIRGs), namely CCDC69, PPP1R16B, IL21R, and FOXP3, were obtained using five machine-learning algorithms. Subsequently, nomogram models were constructed to predict the incidence of Her2-positive breast cancer patients. The outer datasets and receiver operating characteristic curve analysis were used to validate the accuracy of the four M1 MIRGs and nomogram models. The average value of the area under the curve for the nomogram models was higher than 0.75 in both the training and testing sets. After that, survival analysis showed that higher expression of CCDC69, PPP1R16B, and IL21R were associated with overall survival of Her2-positive breast cancer patients. The expression of CCDC69 and PPP1R16B could lead to more benefits than the expression of IL21R and FOXP3 for immunotherapy. Lastly, we conducted immunohistochemistry staining to validate the aforementioned results. In conclusion, we found four M1 MIRGs that may be helpful for the diagnosis, prognosis, and immunotherapy of Her2-positive breast cancer.

关键词： Her2-positive breast cancer bioinformatics analysis M1 macrophage infiltration Machine learning Immunotherapy

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BMC PREGNANCY AND CHILDBIRTH 2025年第1期25卷 1-15页

作者： He, Lidan Zhan, Feng Li, Xuemei Yang, Huijuan Wu, Jianbo Fujian Med Univ Affiliated Hosp 1 Dept Obstet & Gynecol Fuzhou 350004 Fujian Peoples R China Taiyuan Univ Sci & Technol Sch Elect Informat Engn Taiyuan 030024 Shanxi Peoples R China Fujian Jiangxia Univ Coll Engn Fuzhou 350108 Peoples R China

IntroductionPreeclampsia (PE) is a severe pregnancy complication with limited early diagnostic and therapeutic options. Ferroptosis, an iron-dependent cell death pathway, has emerged as a potential mechanism in PE pathogenesis. This study investigated ferroptosis-related genes (FRGs) in PE to identify diagnostic biomarkers and therapeutic *** expressed genes were identified from GEO databases and intersected with FRGs. Hub genes were selected using RandomForest and LASSO algorithms. Their diagnostic potential was evaluated through ROC analysis. Regulatory networks were constructed using transcription factors, microRNAs and potential drug targets. Hub gene expression was validated through immunohistochemistry, Western blot, and RT-qPCR in placental tissues and hypoxic *** identified 25 ferroptosis-related differentially expressed genes enriched in ferroptosis and HIF-1 pathways. Four hub genes (NDRG1, P4HA1, LDHA, and IDO1) showed high diagnostic efficiency (AUC=0.9182). Immune cell analysis revealed altered levels of plasma cells, CD8+ T cells, Tregs, monocytes, and M2 macrophages in PE, correlating significantly with hub gene expression. We identified 84 mRNA-miRNA and 119 mRNA-TF interactions. Among 19 potential drugs, Tetrahydro-NAD showed promising targeting potential. Experimental validation confirmed elevated expression of NDRG1, P4HA1, and LDHA, and decreased IDO1 in PE tissues and hypoxic *** study identified four FRGs as potential PE biomarkers and therapeutic targets, providing new insights into PE pathogenesis through integrated bioinformatics and experimental validation. These findings may facilitate early PE diagnosis and treatment development.

关键词： Preeclampsia Ferroptosis Oxidative stress bioinformatics analysis Experimental validation Drug prediction

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Targeted gene sequencing and bioinformatics analysis of patients with gallbladder neuroendocrine carcinoma:A case report

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 239-251页

作者： Yun-Chuan Yang Zhi-Tao Chen Da-Long Wan Hui Tang Mu-Lin Liu Department of Medical College Jinan UniversityGuangzhou 510000Guangdong ProvinceChina Department of General Surgery The First Affiliated Hospital of Bengbu Medical UniversityBengbu 233000Anhui ProvinceChina Department of Hepatobiliary Surgery Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical CollegeHangzhou 310022Zhejiang ProvinceChina Department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina Department of Pathology The First Affiliated Hospital of Medical School of Zhejiang UniversityHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor *** its clinical severity,the genetic alterations,mechanisms,and signaling pathways underlying gallbladder NEC remain *** SUMMARY This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient,who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and *** gene sequencing and bioinformatics analysis tools,including STRING,GeneMANIA,Metascape,TRRUST,Sangerbox,cBioPortal and GSCA,were used to analyze the biological functions and features of mutated genes in gallbladder *** mutations(APC,ARID2,IFNA6,KEAP1,RB1,SMAD4,TP53,BTK,GATA1,GNAS,and PRDM3)were identified,and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing.A protein-protein interaction network showed significant interactions among the twelve mutated *** Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and *** results revealed 40 tumor-related pathways.A key regulatory factor for gallbladder NEC-related genes was identified,and its biological functions and features were compared with those of gallbladder *** Gallbladder NEC requires standardized *** with other gallbladder carcinomas revealed clinical phenotypes,molecular alterations,functional characteristics,and enriched pathways.

关键词： Gallbladder neuroendocrine carcinoma Targeted-gene sequencing bioinformatics analysis case report Immunocytochemistry Case report

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Identification of Anoikis-Related Genes in Chronic Kidney Disease Based on bioinformatics analysis Combined with Experimental Validation

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JOURNAL OF INFLAMMATION RESEARCH 2025年 18卷 973-994页

作者： Liu, Hong Mei, Manxue Zhong, Hua Lin, Shuyin Luo, Jiahui Huang, Sirong Zhou, Jiuyao Guangzhou Univ Chinese Med Sch Pharmaceut Sci Dept Pharmacol Guangzhou Peoples R China Shandong First Med Univ Affiliated Hosp 1 Dept Gerontol Jinan Peoples R China Shandong Prov Qianfoshan Hosp Jinan Peoples R China

Background: Chronic kidney disease (CKD) is a progressive condition that arises from diverse etiological factors, resulting in structural alterations and functional impairment of the kidneys. We aimed to establish the Anoikis-related gene signature in CKD by bioinformatics analysis. Methods: We retrieved 3 datasets from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Set Enrichment analysis (GSEA) and Gene Set Variation analysis (GSVA) of them, which were intersected with Anoikis-related genes (ARGs) to derive Anoikis-related differentially expressed genes (ARDEGs). Besides, we conducted weighted gene co-expression network analysis (WGCNA) to identify hub genes. And then, we adopted the quantitative real-time PCR (RT-qPCR) assay to validate the hub genes among several CKD animal models. Furthermore, we constructed a competitive endogenous RNA (ceRNA) network for the hub genes utilizing the ENCORI and miRDB databases, while also calculating Spearman correlation coefficients. Ultimately, we applied the CIBERSORTx algorithm to conduct immune infiltration analysis, classifying immune characteristics based on the abundance of 22 immune cell types. Results: To summarize, we identified 13 ARDEGs. WGCNA yielded 6 hub genes, all of which demonstrated significant diagnostic potential in univariate logistic regression analysis (P< 0.05). The principal pathways enriched were involved in cell cycle progression Toxoplasmosis, Cell adhesion molecules, Influenza A, Pathogenic Escherichia coli infection, Small cell lung cancer, Amoebiasis, TNF signaling pathway, and Leukocyte transendothelial migration. Notably, 6 immune cell types exhibited significant differences (P< 0.05) across subgroups with distinct immune characteristics. Moreover, 2 hub genes showed significant variations (P< 0.05) across these immune characteristic subtypes. Among the 4 t

关键词： chronic kidney disease bioinformatics analysis anoikis biomarkers

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Identification of RTP4 facilitating ovarian cancer by bioinformatics analysis and experimental validation

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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 2025年第3期398卷 2665-2675页

作者： Fang, Chunyun Han, Wenling Tang, Chen Shen, Junjing Ni, Bin Gannan Med Univ Dept Obstet & Gynecol Affiliated Hosp 1 Ganzhou 341000 Jiangxi Peoples R China Gannan Med Univ Dept Pharm Affiliated Hosp 1 128 Jinling Rd Ganzhou 341000 Jiangxi Peoples R China

Ovarian cancer (OV) is the most malignant gynecological tumor in women, with poor prognosis and high mortality rate. This study aims to identify hub genes in OV and explore the role of Receptor transporter 4 (RTP4) in OV progression. Common differentially expressed genes (DEGs) were screened from two microarray datasets. GO and KEGG enrichment analysis were performed. Protein-protein interaction (PPI) network was constructed by STING. Kaplan-Meier plotter was used to analyze prognosis. The effect of target gene on immune infiltration was analyzed by TIMER. The proliferation, migration, and invasion of OV cells were measured by CCK-8, wound healing assay, and trans-well assay, respectively. A total of 293 common DEGs were selected from GSE12470 and GSE16709 datasets. Hub genes, EPCAM, KIFC1, RTP4, TAGLN, and ZFP36 were selected by PPI network. Kaplan-Meier plotter demonstrated that high expression of RTP4 was related to low overall survival in OV patients. The TIMER result showed that high expression of RTP4 promoted immune infiltration of CD8+ T cells, B cells, neutrophils, and dendritic cells in OV. Moreover, silencing RTP4 significantly inhibited the proliferation, migration, and invasion of OV cells. RTP4 was associated with the poor prognosis in OV. In summary, silencing RTP4 inhibited the proliferation, migration, and invasion of OV cells, having the potential to be a novel therapeutic target for OV.

关键词： bioinformatics analysis Ovarian cancer Hub genes RTP4 Prognostic marker

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