Frontiers in Genetics最新文献

{"title":"Association between <i>LRRK2</i> gene polymorphisms and Parkinson's disease progression in a Chinese Han population.","authors":"Zhaoting Zhang, Lei Geng, Jiuxin Gao, Ruifang She, Zhonglin Ge, Jianhua Liu, Qianqian He, Bing Fu, Weiguo Liu","doi":"10.3389/fgene.2025.1662348","DOIUrl":"https://doi.org/10.3389/fgene.2025.1662348","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to investigate the association between <i>LRRK2</i> gene polymorphisms and Parkinson's disease (PD) risk, as well as the progression of PD, in a Chinese Han population.</p><p><strong>Methods: </strong>A case-control study was carried out on 180 PD patients and 196 healthy controls between October 2019 and October 2023. The demographic and clinical data of all participants were collected. At the baseline and 3-year follow-up, assessment of motor and non-motor symptoms of PD patients were carried out using scales including Unified Parkinson's Disease Rating Scale parts II, III, and IV, Hoehn and Yahr (H-Y) staging scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Non-motor Symptom Questionnaire, Parkinson's disease sleep scale, Montreal Cognitive Assessment, and Mini-Mental State Examination. Six single nucleotide polymorphisms (SNPs) of the <i>LRRK2</i> gene rs1994090, rs2046932, rs2708453, rs34778348, rs4768212, and rs7304279 were selected and genotyped using the MassARRAY platform in all participants.</p><p><strong>Results: </strong>A strong linkage disequilibrium was observed among the five SNP loci of the <i>LRRK2</i> gene, including rs1994090, rs2046932, rs2708453, rs4768212, and rs7304279. <i>LRRK2</i> rs7304279 (OR = 3.572, P < 0.001) and rs34778348 (OR = 0.408, P = 0.003) contributed to the risk of PD development. Carriage of more risk variants were associated with higher risk of PD (OR = 6.467, P < 0.001). Cox proportional hazards model analysis showed that <i>LRRK2</i> rs7304279 polymorphism was significantly associated with H-Y stage progression (<i>P</i> = 0.030).</p><p><strong>Conclusion: </strong>Our findings suggest that <i>LRRK2</i> rs34778348 and rs7304279 polymorphisms are associated with the risk of developing PD. And <i>LRRK2</i> rs7304279 polymorphism is correlated with disease progression in PD patients.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1662348"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-modal predictive modeling of multi-omic data in 3D airway organ tissue equivalents during viral infection.","authors":"Mostafa Rezapour, Patrick M McNutt, David A Ornelles, Stephen J Walker, Sean V Murphy, Anthony Atala, Metin Nafi Gurcan","doi":"10.3389/fgene.2025.1658577","DOIUrl":"https://doi.org/10.3389/fgene.2025.1658577","url":null,"abstract":"<p><strong>Introduction: </strong>Developing robust predictive models from multi-omics data is challenging because sample sizes are typically small (often fewer than 100) while the feature space is vast (over 20,000 molecular features such as genes, transcripts, and proteins), which increases the risk of overfitting and limits generalizability. To address this challenge, this study introduces the Magnitude-Altitude Score Analysis for Tracking Infection and Time-Dependent Genes (MASIT), a novel method adept at filtering out irrelevant features/genes while focusing on important ones.</p><p><strong>Methods: </strong>Applied to the 3D airway organ tissue equivalent model that mimics human airway physiology, MASIT employed both RNA-Seq and NanoString technologies for a comprehensive analysis. RNA-Seq offered a transcriptomic overview of 19,671 protein coding genes, whereas NanoString targeted 773 specific genes. We used MASIT to analyze gene expression changes in the airway tissue equivalent after exposure to Influenza A virus, Human metapneumovirus, and Parainfluenza virus type 3 at 24- and 72-hour post-infection. MASIT was trained and validated on NanoString data, tested on the held-out RNA-Seq test set, and benchmarked against widely used feature selection approaches, including Fisher score, minimum Redundancy Maximum Relevance, embedded Lasso regression, and Boruta feature importance.</p><p><strong>Results: </strong>MASIT achieved a 92% accuracy in differentiating eight groups of infected samples. Our findings showed that MASIT outperformed models using the full gene set, notably in algorithms like Random Forest, XGBoost, and AdaBoost. Selected genes such as IFIT1, IFIT2, IFIT3, OASL, IFI44, and OAS3 were particularly effective in categorizing samples by viral type and infection stage. Benchmarking further demonstrated that MASIT not only exceeded the performance of existing feature selection methods within NanoString data but also uniquely maintained high accuracy and stability when applied to held-out RNA-Seq data.</p><p><strong>Discussion: </strong>These results provide insights into the host's molecular response to viral infections and highlight MASIT as a robust tool for analyzing high-dimensional, small-sample multi-omics datasets.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1658577"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MK2-mediated AKT/MYC signaling activation promotes epithelial-mesenchymal transition in lung adenocarcinoma.","authors":"Rong Qi, Chen Fang, Penghui Liu, Weiguo Gu, Chao Shi, Guohua Zhang, Feng Qiu","doi":"10.3389/fgene.2025.1615018","DOIUrl":"https://doi.org/10.3389/fgene.2025.1615018","url":null,"abstract":"<p><strong>Purpose: </strong>The protein kinase Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) is linked to higher risks of metastasis and mortality in some cancers. Nonetheless, its precise function in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore MK2's function in LUAD cells and identify the underlying molecular mechanisms.</p><p><strong>Methods: </strong>MK2 expression in LUAD patients was confirmed through Timer2.0 database and tissue microarrays. Immunohistochemical staining for MK2 was performed on LUAD samples to investigate its association with metastasis and invasion. The activity of MK2 was inhibited in LUAD cell lines A549 and H358 using a specific MK2 inhibitor. Subsequently, cell viability, migration, and invasion were assessed. Gene expression changes were confirmed through Western blotting. Additionally, an AKT activator was used to validate the role of the MK2-regulated AKT/MYC signaling pathway.</p><p><strong>Results: </strong>MK2 expression is significantly higher in LUAD tissues compared to adjacent normal tissues. Reducing MK2 activity not only curtails cell proliferation, migration, and EMT-related invasion <i>in vitro</i> but also disrupts the AKT/MYC signaling axis. Activation of the AKT/MYC pathway can counteract the inhibitory effects of MK2 suppression.</p><p><strong>Conclusion: </strong>Our findings suggest that MK2 promotes migration and invasion in LUAD through the AKT/MYC signaling pathways, positioning MK2 as a potential therapeutic target in LUAD treatment.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1615018"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concordance of an in-house 2-steps PCR-SSP and nanopore sequencing for <i>HLA-B*57:01</i> and <i>HLA-B*58:01</i> typing: a comparative study.","authors":"Nattapong Intharuangrung, Chonticha Sirikul, Pattaraporn Nimsamer, Thidathip Wongsurawat, Auttachai Saejia, Nampeung Anukul","doi":"10.3389/fgene.2025.1649990","DOIUrl":"https://doi.org/10.3389/fgene.2025.1649990","url":null,"abstract":"<p><p>This study reports an optimized in-house 2-step PCR-SSP assay for rapid, cost-effective detection of <i>HLA-B*57:01</i> and <i>HLA-B*58:01</i> in routine pharmacogenomics laboratory. This assay employs allele-specific primers positioned within exon 2-3 boundaries, validated <i>in silico</i> against common <i>HLA-B</i> alleles. Using 30 clinical DNA samples, our PCR workflow (<1 h) showed 100% concordance at 2-field resolution with Oxford Nanopore sequencing performed using ligation-based sequencing kit with PCR barcoding. Cohen's kappa was 1.00 with 95% CI. The turnaround time and reagent cost per sample were reduced to 1 h of hands-on PCR time and USD 7 per sample, respectively. These do not include DNA extraction or gel electrophoresis analysis. This 2-step PCR-SSP offers a robust alternative for pharmacogenomic screening in resource-limited settings for detecting the <i>HLA-B*57:01</i> and <i>HLA-B*58:01</i>.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1649990"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of circular RNAs in diabetic cardiomyopathy: biological characteristics and clinical prospects.","authors":"Yunfei Guan, Quancheng Han, Meng Wang, Jianguo Xu, Xiujuan Liu","doi":"10.3389/fgene.2025.1665571","DOIUrl":"https://doi.org/10.3389/fgene.2025.1665571","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is a specific form of heart disease induced by diabetes, characterized by myocardial fibrosis, oxidative stress, metabolic dysregulation, and cardiomyocyte death. In recent years, circular RNAs (circRNAs), a novel class of non-coding RNAs, have gained increasing attention due to their unique covalently closed structure, high stability, and critical regulatory roles in various diseases. While extensive studies have been conducted on microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in the context of DCM, research on circRNAs remains relatively limited and fragmented. Existing reviews often focus on specific aspects without providing a systematic and comprehensive overview. This review aims to summarize the current progress in circRNA research related to DCM, with a particular focus on the molecular mechanisms and regulatory networks through which circRNAs influence metabolic disorders, oxidative stress, myocardial fibrosis, and programmed cell death. In addition, the potential of circRNAs as diagnostic biomarkers and therapeutic targets is evaluated, along with an in-depth discussion of current challenges and future research directions. This work is intended to offer theoretical insights and reference value for both fundamental and translational studies of circRNAs in DCM.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1665571"},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrauterine phenotype, genetic analysis, and pregnancy follow-up of fetuses with the 16p12.2 microdeletion.","authors":"Meiying Cai, Na Lin, Hailong Huang, Wenqiang You, Nan Guo, Liangpu Xu","doi":"10.3389/fgene.2025.1595399","DOIUrl":"https://doi.org/10.3389/fgene.2025.1595399","url":null,"abstract":"<p><p>Reports on the intrauterine phenotype of the 16p12.2 microdeletion are few. A retrospective analysis of the clinical data, genetic testing results, and neonatal prognoses of fetuses with the 16p12.2 microdeletion was conducted to provide a basis for their clinical management. The research participants were pregnant women who underwent prenatal diagnoses between November 2016 and June 2024. Among them, 12,000 cases were selected for karyotype analyses and single-nucleotide polymorphism (SNP) array testing. In the SNP array, 13 out of 12,000 fetuses (0.1%) had the 16p12.2 microdeletion, which included 6 cases of distal deletions and 7 of proximal deletions, involving fragment sizes ranging from 511 to 994 kb. The 16p12.2 distal deletion mainly involves the <i>OTOA</i> gene, whereas the 16p12.2 proximal deletion mainly involves the <i>EEF2K</i> and <i>CDR2</i> genes. Among the 13 fetuses, five exhibited intrauterine phenotypes, including a small biparietal diameter, head circumference cerebellar dysplasia, corpus callosum dysplasia, small abdominal circumference, mild ventriculomegaly, left ventricular hyperechoic foci, small kidney measurements, nasal bone dysplasia, and polyhydramnios. The inheritance testing of six cases revealed that one case was <i>de novo</i> and five were inherited from the father/mother with normal phenotypes. Except for one case of early abortion, two cases of fetal ultrasound abnormality-led terminations, and one of adverse pregnancy history-based termination, the remaining nine cases included full-term delivery and no significant abnormalities in the birth conditions. One case was lost at follow-up during a phone call 6 months after birth, and the remaining eight infants did not show any significant abnormalities during follow-up. The SNP array effectively diagnosed the 16p12.2 microdeletion, recognized its range and associated genes, and improved the prenatal diagnoses. Thirteen 16p12.2 microdeletion-carrying fetuses lacked intrauterine-specific phenotypes, and eight showed no abnormalities during the most recent postnatal follow-up. However, considering delays in the children's hearing and neurological development, it is important to conduct continuous and regular post-birth follow-ups. When 16p12.2 deletions are inherited or restricted to distal regions, they often exhibit reduced penetrance. This underscores the need for cautious interpretations of prenatal genetic data.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1595399"},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying metabolism-related genes in liver cancer through weighted gene co-expression network analysis and machine learning.","authors":"Taorui Wang, Zijun Lai, Shengjun Tang, Lehang Lin, Mingjiao Zhang","doi":"10.3389/fgene.2025.1654459","DOIUrl":"https://doi.org/10.3389/fgene.2025.1654459","url":null,"abstract":"<p><strong>Objective: </strong>As a leading cause of cancer-related mortality, liver cancer was associated with metabolic dysregulation. We aimed to identify metabolism-related prognostic biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>Transcriptomic data from TCGA were analyzed using EdgeR to identify differentially expressed genes (DEGs). WGCNA was applied to unveil the metabolism-related genes in liver cancer. Machine learning algorithms (RF, SVM, LASSO) refined marker genes. GSEA and ssGSEA were conducted to identify pathway associations and immune interactions of marker genes. DGIdb database predicted candidate therapeutics targeting these biomarkers. The independent queue (GSE54236) was verified as an external dataset. RT-PCR validated gene expression in clinical samples.</p><p><strong>Results: </strong>A total of 234 metabolism-related genes were identified in liver cancer. Through undergoing machine learning by RF, SVM, and LASSO algorithms, seven marker genes (ACADS, ALDH8A1, COX4I2, CYP2C8, DBH, NDST3, and PLA2G6) were obtained. Except for PLA2G6, the other genes were correlated with the survival of patients with liver cancer and immune cells infiltration. Additionally, ACADS, ALDH8A1, CYP2C8, DBH, and NDST3 were downregulated, and COX4I2 was upregulated in dataset of GSE54236, which were consist with those in TCGA database. However, RT-PCR validation in 10 paired clinical samples confirmed significant downregulation of ACADS, ALDH8A1, COX4I2, CYP2C8, DBH, and NDST3 in tumor tissues (all P < 0.05). Immune infiltration analysis revealed these genes might influence immune cell infiltration in the tumor microenvironment. And the candidate drugs were unveiled, including PAZOPANIB, SUMATRIPTAN, ETOPOSIDE, etc.</p><p><strong>Conclusion: </strong>The metabolism-related biomarkers ACADS, ALDH8A1, COX4I2, CYP2C8, DBH, and NDST3 demonstrated significant potential for predicting liver cancer prognosis and may serve as candidate therapeutic targets.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1654459"},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: a family report of hereditary pancreatitis caused by SPINK1 and PRSS1 gene mutations.","authors":"Jing Xu, Ying Hu, Banghui Xiao, Juan He, Miao Zhang, Rui Wang, Nianchun Peng","doi":"10.3389/fgene.2025.1610108","DOIUrl":"https://doi.org/10.3389/fgene.2025.1610108","url":null,"abstract":"<p><p>Hereditary pancreatitis (HP) is a rare genetic disorder of the pancreas. We report a case of a 20-year-old woman presenting with classic features of lean diabetes mellitus, chronic diarrhea, and diabetic ketoacidosis but notably without abdominal pain. Imaging revealed pancreatic calcification. Genetic testing identified pathogenic compound mutations in SPINK1 (c.194+2T>C) and PRSS1 (c.623G>C), confirming a diagnosis of HP. Family screening showed her mother carried a homozygous <i>SPINK1</i> mutation, while her siblings variably carried heterozygous <i>SPINK1</i> and/or <i>PRSS1</i> mutations. All family members with both variants, except the third sister, had pancreatic calcifications. Diabetes was observed in the proband, her mother, and her first and second sisters. This case highlights that in patients under 25 years of age presenting with lean body habitus, diarrhea or steatorrhea, poor islet function, and a family history of diabetes-despite lacking overt abdominal pain-HP should be considered as a differential diagnosis.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1610108"},"PeriodicalIF":2.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-generation sequencing of mitochondrial DNA reveals pathogenic variants and protective haplogroup D4 in esophageal cancer.","authors":"Xiucheng Jiang, Lan Shi, Mei Zhao, Cui Chen, Tao Tang, Simeng Ji, Bingbing Lv, Lihua Jia, Shuhan Duan, Jinyue Ma, Jiyu Pang, Bo Mu, Yongsheng Zhao, Junbao Yang","doi":"10.3389/fgene.2025.1643229","DOIUrl":"10.3389/fgene.2025.1643229","url":null,"abstract":"<p><strong>Introduction: </strong>The germline variations in the mitochondrial genome of esophageal cancer (EC) remain uncertain. Our study aimed to explore the distribution and pathogenicity of mitochondrial genome variations in EC, as well as to identify haplogroups associated with the development of EC.</p><p><strong>Methods: </strong>We performed next-generation sequencing of the mitochondrial genomes from peripheral blood samples of 146 EC patients and 120 healthy controls. Variant annotation was performed using MitoMap, while pathogenicity prediction was conducted through tools such as MitoTip, SIFT, and PolyPhen2. Moreover, haplogroup classification was carried out using the Haplogrep3 platform.</p><p><strong>Results: </strong>A total of 1299 mitochondrial variants were identified among 146 EC patients, including 171 novel (previously unreported) mutations. Compared with the healthy control group, the EC cohort exhibited a higher frequency of variants in genes such as ND2, COX1, COX2, 12S rRNA, and 16S rRNA. Three tRNA mutations (7496_T>C, 5771_A>G, and 5613_T>A) were predicted to be potentially pathogenic. Within the protein-coding regions, 14 variants were classified as deleterious based on predictions from 13 independent bioinformatic algorithms. Notably, mitochondrial haplogroup D4 was significantly associated with a decreased risk of developing EC. Furthermore, several mtDNA single-nucleotide polymorphisms (SNPs), including 302_A>AC, 1824_T>C, 1842_A>G, 3010_G>A, 8414_C>T, and 14668_C>T, showed significant associations with EC susceptibility.</p><p><strong>Conclusion: </strong>We found that the number of variations in multiple regions of the mitochondrial genome in the EC population was higher than that in the control group. Additionally, several potentially pathogenic variants were identified, and haplogroup D4 was suggested as a potentially protective haplogroup against the development of EC.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1643229"},"PeriodicalIF":2.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constructing a novel mitochondrial-related gene signature for predicting survival and evaluating the tumor immune microenvironment in clear cell renal cell carcinoma.","authors":"Jiaxuan Qin, Lijian Zhang, Bowen Chen","doi":"10.3389/fgene.2025.1543593","DOIUrl":"10.3389/fgene.2025.1543593","url":null,"abstract":"<p><strong>Background: </strong>Mitochondria play an important role in tumors. Cellular energy supply, signaling, metabolism, autophagy, aging, and tumorigenesis are all associated with mitochondria. However, we lack a reliable prognostic model using mitochondrial-related genes in clear cell renal cell carcinoma (ccRCC).</p><p><strong>Methods: </strong>A systematic analysis of available TCGA databases and related studies was conducted using the R language and online analysis tools to evaluate the prognostic value of mitochondrial-related genes and the tumor microenvironment in ccRCC.</p><p><strong>Results: </strong>We constructed a novel mitochondrial-related gene signature for predicting survival and evaluating the tumor immune microenvironment in ccRCC. The mitochondrial-related gene signature included MICALL2, FKBP10, and ACADSB. According to the risk score of the risk model, ccRCC patients were divided into high- or low-risk groups. The ccRCC high-risk group with a high-risk score is related to poor prognosis and poor efficacy from immune checkpoint inhibitors (ICIs).</p><p><strong>Conclusion: </strong>Our mitochondrial-related gene signature, as a risk model, could be a reliable ccRCC prognostic biomarker and could predict the response to immunotherapy. The risk score was correlated with the tumor microenvironment and immune cell infiltration.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1543593"},"PeriodicalIF":2.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12497594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}