Human Gene最新文献

{"title":"Identification and functional characterization of two novel SRD5A2 variants in Iranian siblings with 5α-reductase type 2 deficiency: Expanding the mutational spectrum and implications for genetic diagnosis","authors":"Mahtab Ordooei ,&nbsp;Nasrin Zamani ,&nbsp;Bahareh Rabbani ,&nbsp;Nejat Mahdieh","doi":"10.1016/j.humgen.2025.201389","DOIUrl":"10.1016/j.humgen.2025.201389","url":null,"abstract":"<div><div>Disorders of sex development (DSD) represent a diverse group of congenital conditions that disrupt the typical development of sexual tissues due to various genetic anomalies. Among these, 5α-reductase type 2 deficiency, caused by mutations in the <em>SRD5A2</em> gene, impairs the conversion of testosterone to dihydrotestosterone (DHT), essential for male genital differentiation. In this study, we describe two sisters from an Iranian consanguineous family, both presenting with 46,XY DSD due to two novel variants in <em>SRD5A2</em> gene.</div><div>Clinical evaluations, biochemical testing, and karyotyping were conducted for the patients. Clinical evaluations, including karyotyping and biochemical analyses, revealed a 46,XY karyotype and significantly elevated testosterone-to-DHT ratios in both patients, raising suspicion of 5α-reductase deficiency. The coding regions of the <em>SRD5A2</em> gene were sequenced for the affected siblings and their parents, and a thorough search using targeted keywords was conducted to identify previously reported intronic variants in this gene.</div><div>Molecular genetic testing identified two novel homozygous variants in the <em>SRD5A2</em> gene: c.314G&gt;C, p.(Arg105Thr) and c.445+5G&gt;C. Segregation analysis confirmed that the parents were heterozygous carriers for these variants. In silico predictions and bioinformatics analyses suggest that the p.(Arg105Thr) variant destabilizes the protein structure, alters its charge, and increases its molecular flexibility, likely contributing to the disease phenotype. Additionally, the c.445+5G&gt;C variant, located within a splice motif, may disrupt normal splicing, further implicating it in the pathogenesis of the disorder. To date, twelve intronic variants have been reported in <em>SRD5A2</em>, suggesting that intronic mutations may significantly impact its function.</div><div>This study underscores the importance of early genetic diagnosis in DSD, particularly in populations with high rates of consanguinity, to enable timely intervention. The novel variants reported here expand the mutational spectrum of <em>SRD5A2</em> and highlight the utility of comprehensive genetic and bioinformatic analyses in understanding the molecular underpinnings of DSD.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201389"},"PeriodicalIF":0.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring preservation of autism spectrum disorder dysregulated co-expression modules in accessible cell models","authors":"Camily E.F. Rodrigues,&nbsp;Bruna G.G. Pinto,&nbsp;Karina Griesi-Oliveira","doi":"10.1016/j.humgen.2024.201366","DOIUrl":"10.1016/j.humgen.2024.201366","url":null,"abstract":"<div><div>Introduction: Autism spectrum disorder (ASD) affects more than 1 % of the population, and there is no biomarker to diagnose this condition. Dysregulation of co-expressed gene modules has been observed in neuronal cells of ASD individuals, suggesting that the expression profile of these genes could be used as a biomarker for the disorder. Brain tissue biopsy is impractical, and neuron acquisition through cell reprogramming is resource-intensive. Objectives: Identify accessible cell models reflecting co-expression modules that are dysregulated in ASD neuronal cells. Methods: Three groups of neuronal modules previously implicated in ASD (synapse, immune response, and translation modules) were assessed for preservation in transcriptomes from peripheral blood, urine-derived epithelial cells (UEC), umbilical cord blood (UCB) and dermal papilla stem cells (DPSC), using WGCNA (weighted gene co-expression analysis). Results: Thirteen studies (blood [5], UEC [2], DPSC [2], UCB [4]) were analyzed. The ASD-associated modules related to translation and immune response have showed a consistent moderate preservation in UEC and blood transcriptome studies. Despite moderate preservation, validation analysis using ASD blood transcriptome data revealed no significant differences between ASD individuals and controls. This result may be explained by the lack of preservation in selected studies, potentially influenced by technical factors. Our findings suggest that further validation is necessary, particularly focusing on protocol consistency and data processing, as accessible tissues like UEC and blood may offer a promising direction for developing non-invasive biomarkers for ASD.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201366"},"PeriodicalIF":0.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulated expression of DDR2 and MYLK correlates with poor prognosis in colorectal tumours","authors":"Steffie Urmila Avanthi ,&nbsp;Sonali Mondkar ,&nbsp;Venkat Rao G ,&nbsp;Pradeep Rebala ,&nbsp;Sanjeev M. Patil ,&nbsp;Mahesh Shetty ,&nbsp;Mitnala Sasikala ,&nbsp;Anuradha Sekaran ,&nbsp;Nageshwar Reddy D ,&nbsp;Rajasekhar Pinnamaneni ,&nbsp;Ravikanth Vishnubhotla","doi":"10.1016/j.humgen.2024.201358","DOIUrl":"10.1016/j.humgen.2024.201358","url":null,"abstract":"<div><h3>Background</h3><div>Optimal response to conventional treatment strategies in treating colorectal cancer (CRC) is not attained in a substantial proportion of patients. This leads to unnecessary side effects, higher risk of recurrence ultimately leading to a poor 5-year survival. Instead, targeting upregulated genes with known functions in tumour progression/recurrence with approved drugs may be a superior alternate to minimize the risk of progression. We therefore performed global gene expression in tumours with CRC, identified upregulated genes, shortlisted and replicated 3 genes with approved drugs in an independent cohort.</div></div><div><h3>Materials and methods</h3><div>A total of 123 tumours with colorectal cancer were collected in RNALater from patients undergoing treatment primarily by surgery after obtaining written informed consent. RNA was isolated (Qiagen RNAeasy), assessed for quality and transcriptome sequencing (<em>N</em> = 20) performed on Illumina HiSeqX. Data were analysed using The Galaxy platform and dysregulated genes identified. Approved drugs for the upregulated genes were retrieved from The Drug Gene Interaction Database. Relative gene expression of top three upregulated genes (<em>DDR2, AXL</em> and <em>MYLK</em>) were replicated in an independent tumour cohort (<em>N</em> = 103). Control tissues (<em>N</em> = 5) were collected from patients undergoing surgery for reasons other than malignancy.</div></div><div><h3>Results</h3><div>The mean age of the study group was 54.98 ± 11.80 years that predominantly (75.67 %) comprised of males. Most of the tumours were in the ascending colon (30.10 %) or in rectosigmoid (29.13 %), moderately differentiated adenocarcinomas (77.67 %) in the 2 A stage (46.60 %) or 3B stage (41.75 %). While, 24/103 (23.30 %) tumours showed upregulation of <em>DDR2</em>, 18 (17.47 %) and 16 (15.53 %) tumours showed upregulation of <em>AXL</em> and <em>MYLK</em> genes respectively. Upregulation of <em>DDR2</em> and <em>MYLK</em> genes were associated with presence of tumour deposits (OR– 4.86; 95 % CI: 1.83–12.94; <em>p</em> = 0.001 and OR– 2.73; 95 % CI: 0.87–8.55; <em>p</em> = 0.08 respectively).</div></div><div><h3>Conclusion</h3><div>We demonstrate the upregulation of <em>DDR2</em> and <em>MYLK</em> genes in a sizeable proportion of tumours that were associated with tumour deposits. Tumour deposits are associated with poor prognosis and therefore targeting the tumours with specific approved drugs might reduce the risk of progression and benefit the patient.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201358"},"PeriodicalIF":0.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MALAT1 and BCYRN1 lncRNAs expression in patients with breast cancer from Northwest Iran","authors":"Alireza Ahmadi,&nbsp;Amin Moqadami,&nbsp;Mohammad Khalaj-Kondori,&nbsp;Mohammad Ali Hosseinpour Feizi","doi":"10.1016/j.humgen.2024.201370","DOIUrl":"10.1016/j.humgen.2024.201370","url":null,"abstract":"<div><h3>Introduction</h3><div>Abnormally expressed lncRNAs in cancer tissues can potentially play as biomarkers for cancer diagnosis, prognosis, and treatment. This study aimed to assess the expression and biomarker potential of <em>MALAT1</em> and <em>BCYRN1</em> in breast cancer (BC).</div></div><div><h3>Methods</h3><div>Seventy paired samples of cancerous and non-cancerous adjacent tissues from breast cancer patients were collected and used for RNA extraction and cDNA synthesis. The expressions of <em>MALAT1</em> and <em>BCYRN1</em> lncRNAs were evaluated by qRT-PCR. In addition, the correlation between the expression levels of <em>MALAT1</em> and <em>BCYRN1</em> was investigated.</div></div><div><h3>Results</h3><div>The qRT-PCR results revealed that <em>MALAT1</em> and <em>BCYRN1</em> levels were considerably elevated in tumor tissues compared to the marginal samples of BC patients. Furthermore, <em>MALAT1</em> expression was extremely correlated with tumor stages (<em>p</em> = 0.031). ROC curve analysis indicated that <em>BCYRN1</em> might be considered a potential biomarker for BC, while <em>MALAT1</em> showed poor results in this study. In addition, there was a statistically non-significant positive correlation between <em>MALAT1</em> and <em>BCYRN1</em> expression levels.</div></div><div><h3>Conclusion</h3><div>In conclusion, the expression levels of <em>MALAT1</em> and <em>BCYRN1</em> lncRNAs were significantly upregulated in breast cancer tissues compared to normal margins.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201370"},"PeriodicalIF":0.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facial dysmorphia and genetic disorders in Moroccan children early diagnosis and the role of advanced genetic techniques","authors":"Asmaa Gaadi ,&nbsp;Sara Missaoui ,&nbsp;Hind Dehbi ,&nbsp;Ahmed Aziz Bousfiha ,&nbsp;Mouna Lehlimi","doi":"10.1016/j.humgen.2025.201383","DOIUrl":"10.1016/j.humgen.2025.201383","url":null,"abstract":"<div><h3>Background</h3><div>Genetic diseases pose significant challenges in populations with limited access to advanced diagnostic tools. This study focuses on rare congenital malformations in pediatric cases, emphasizing facial dysmorphia as a crucial indicator for early diagnosis and genetic counseling.</div></div><div><h3>Methods</h3><div>A three-year retrospective study was conducted at the Neonatology Service of the Abderrahim Harouchi Mother and Child Hospital in collaboration with the Department of Medical Genetics. Ten cases were selected for detailed analysis. Advanced genetic diagnostic techniques, including karyotyping, FISH, CGH-array, and whole genome sequencing (WGS), were employed to identify underlying genetic anomalies.</div></div><div><h3>Results</h3><div>Among the 10 analyzed cases, four were from consanguineous families. Genetic anomalies identified included ring chromosome 9, Wolf-Hirschhorn syndrome, and a novel homozygous pathogenic mutation in the <em>FREM1</em> gene. Each diagnosis led to targeted therapeutic interventions tailored to the clinical and genetic findings.</div></div><div><h3>Conclusion</h3><div>This study underscores the importance of advanced genetic diagnostic techniques and a multidisciplinary approach in managing congenital malformations. Early and precise identification of genetic anomalies is essential for improving patient outcomes and offering effective genetic counseling, particularly in regions with a high prevalence of genetic disorders.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201383"},"PeriodicalIF":0.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Appraisal of prolyl 4-hydroxylase alpha subunit gene polymorphisms in Spondyloepimetaphyseal dysplasia of Handigodu type (SEMDHG)","authors":"Pulamaghatta N. Venugopal ,&nbsp;Isukapatla Arjun Rao ,&nbsp;Sahid Afrid Mollick ,&nbsp;Adimoolam Chandrasekar","doi":"10.1016/j.humgen.2025.201387","DOIUrl":"10.1016/j.humgen.2025.201387","url":null,"abstract":"<div><h3>Background</h3><div>The Handigodu variant of Spondyloepimetaphyseal Dysplasia (SEMD_HG) is a severe, progressive osteoarthritic disorder characterized by chronic pain and joint degeneration. Clinically, the disorder presents in three distinct phenotypic forms, each exhibiting varying degrees of stature reduction and disease severity. Urine analysis of affected individuals reveals an elevated peptide-bound proline to 4-hydroxyproline ratio relative to controls, suggesting disruptions in collagen metabolism. Given the critical role of prolyl 4-hydroxylase enzymes in stabilizing collagen structure, this study undertook a comprehensive sequence analysis of all three isoforms of prolyl 4-hydroxylase in both affected and unaffected individuals to elucidate potential molecular underpinnings of the disorder.</div></div><div><h3>Method</h3><div>The entire exonic regions and 2000 base pairs upstream of the translation start sites of the <em>P4HA1</em>, <em>P4HA2</em>, and <em>P4HA3</em> genes were sequenced in a cohort of 300 individuals, comprising 166 affected and 134 unaffected individuals.</div></div><div><h3>Results</h3><div>Sequence analysis of the α (I), α (II), and α (III) subunit genes identified three novel SNPs and a 39-bp deletion variant, in addition to ten previously reported SNPs catalogued in dbSNP. The SNP rs28384495 in <em>P4HA1</em>, the 39-bp deletion variant, and a novel mutation (SNP3) in <em>P4HA3</em> exhibited significantly different allele frequencies between patients and controls. Genotype association analysis revealed that SNPs in <em>P4HA1</em> and <em>P4HA3</em> were associated with Type 2 and Type 3 HD under various genetic models. Notably, all Type 2 HD patients were heterozygous for the 39-bp deletion, whereas all Type 3 HD patients were homozygous for the variant. Haplotype analysis corroborated the findings of the genotype association analysis.</div></div><div><h3>Conclusion</h3><div>This study is the first to account an association between the <em>P4H</em> gene and disease. Further research is needed to evaluate the functional implications of the identified mutations.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201387"},"PeriodicalIF":0.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143264833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin's modulation of gut microbiota and its implications for Non-Alcoholic Fatty Liver Disease(NAFLD): A network pharmacology and molecular dynamics study","authors":"Sarvesh Sabarathinam ,&nbsp;Ramesh Venkatachalapathy ,&nbsp;Akash Jayaraman","doi":"10.1016/j.humgen.2024.201364","DOIUrl":"10.1016/j.humgen.2024.201364","url":null,"abstract":"<div><div>Non-alcoholic fatty liver disease (NAFLD) involves excessive fat accumulation in the liver, with gut microbiota playing a crucial role in its development. Metformin, a common treatment for type 2 diabetes, affects gut microbiota, influencing NAFLD management. This study investigates how metformin modifies gut microbes and how these changes impact bodily functions. Using network pharmacology, molecular docking, and dynamics studies, we identified key target genes linking NAFLD and gut metabolites. Molecular dynamics revealed that AKT1 and HSP0AA1 complexes are stable in solvent environments. Additionally, GO and KEGG pathway analyses indicated that these target genes are involved in lipid metabolism pathways. Our findings enhance the understanding of metformin's impact on NAFLD through gut microbiota modulation.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201364"},"PeriodicalIF":0.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the therapeutic potential of Quercetin and its metabolite (Q3OG) for targeting inflammatory pathways in Crohn's disease: A network pharmacology and molecular dynamics approach","authors":"Sarvesh Sabarathinam","doi":"10.1016/j.humgen.2024.201372","DOIUrl":"10.1016/j.humgen.2024.201372","url":null,"abstract":"<div><div>Crohn's disease is a chronic, inflammatory-mediated condition that calls for an innovative therapeutic approach. Quercetin, a bioactive molecule, has a significant therapeutic impact on chronic illnesses mediated by inflammatory processes. Using the network Pharmacology (NP) based approach, top-ranked targets such as AKT1, MMP9, EGFR, MMP2, TNF, PTGS2, SRC, KDR, PARP1, and MCL1 have been identified. Molecular docking were performed for the AKT1 target towards PDB: <span><span>7NH5</span><svg><path></path></svg></span>, which shows that Q3OG [<strong>Quercetin 3-Glucuronide</strong>] (−10.4 kcal/mol) has stronger binding affinity when compared with <strong>Quercetin</strong> [Q](−8.4 kcal/mol). The Biological process, Cellular component and molecular function was estimated from the network analysis of the Hub-genes. The KEGG enrichment analysis was performed to ensure the enriched targets. To provide a more effective mechanism for demonstrating protein-ligand interaction of Q and Q3OG with Akt1 protein kinase complex were subjected to a molecular dynamic at 300 K for 100 ns. The complex's structural stability, compactness, residual flexibility and hydrogen bond interaction were evaluated. This result inspires hope for future research and prospective therapeutic approaches to identifying lead molecules from quercetin.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201372"},"PeriodicalIF":0.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of Quercetin on microRNAs expression in the breast cancer cell lines: A systematic review","authors":"Niloofar Sharbati ,&nbsp;Mohammad Hossein Dehghan ,&nbsp;Malihe Safavi ,&nbsp;Malihe Farid ,&nbsp;Naghmeh Zhalehjoo","doi":"10.1016/j.humgen.2025.201379","DOIUrl":"10.1016/j.humgen.2025.201379","url":null,"abstract":"<div><div>Although standard therapeutic modalities have significantly improved the treatment of patients with Breast Cancer (BC), BC is the most common leading cause of cancer mortality worldwide. Evidence indicates that Quercetin could inhibit signal transduction, induce cancer cell apoptosis, and suppress proliferation, invasion, and metastases of tumor cells via regulation of microRNA (miRNA) expression. Hence, this study was conducted to systematically assess the effect of Quercetin on miRNA expression in BC cell lines.</div><div>A comprehensive search of electronic databases including Scopus, Cochrane Library, PubMed, and Web of Science was conducted with keywords (i.e., “MicroRNA”,” Quercetin”, “Normal tissue”, “Breast cancer”, “Cell line”, “Apoptosis”, “Survival”, “Prognosis”, “Up-regulation”, “Down-regulation”, “Proliferation”, “Overexpression”, and “Lower expression”) to identify relative articles published until August 2023. Studies that investigated the effects of Quercetin on BC cell lines were included. Data regarding miRNA expression and cell survival were extracted.</div><div>Initially, 6753 studies were retrieved, of which 14 met inclusion criteria. Accordingly, 2 studies were included in the final assessment. The findings of 2 studies revealed that Quercetin could inhibit the progression of BC cell lines through up-regulation of the miR-146a in MCF-7 and MDA-MB-231 cell lines, and down-regulation of miR-21 in MCF-7 cells.</div><div>Our study showed that the inhibition role of Quercetin on BC cell line could be provided via miRNA expression.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201379"},"PeriodicalIF":0.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling of human genes afflicted with nasopharyngeal carcinoma using microarray data","authors":"Rupam Raj ,&nbsp;Subhashini ,&nbsp;Kamalesh Kumar Patel ,&nbsp;Mukesh Kumar","doi":"10.1016/j.humgen.2025.201376","DOIUrl":"10.1016/j.humgen.2025.201376","url":null,"abstract":"<div><div>Background</div><div>Nasopharyngeal carcinoma (NPC) is the most prevalent malignant carcinoma, and yet the biological mechanisms behind its pathogenesis are still unknown.</div><div>Objective</div><div>The objective of the research work was to apply bioinformatics tools to determine the essential expressed genes linked to NPC pathogenesis.</div><div>Material and methods</div><div>We retrieved three datasets (GSE12452, GSE13597, and GSE64634), from the Gene Expression Omnibus (GEO) portal. Differentially expressed genes (DEGs) determined between two groups called normal and NPC tissues. Gene ontology enrichment analysis (GO) performed through the online tool DAVID, and Kyoto Encyclopedia of Genes and Genomes (KEGG) online database used to identify pathways and progressions in which DEGs are highly involved in disease progression.</div><div>Results</div><div>We identified 77 commonly upregulated, 62 common downregulated in total 140 common DEGs in 3 datasets. The key cancer-causing pathways found in our study were mostly regulating cell adhesion molecules, Akt signalling pathway, cell cycle, cytochrome P450 and one carbon pool by folate. The interaction is shown between these DEGs through a protein protein interaction (PPI) network using STRING software and try to understand the effect these genes have on each other and noticed the most influential genes by studying their topological connectivity. The most influential genes, hub genes were identified by creating modules upon analysis of these modules.</div><div>Conclusions</div><div>We got 4 hub genes namely Aurora A (AURKA), Breast cancer susceptibility gene 1 (BRCA1), Fanconi anaemia group I protein (FANCI), and Abnormal spindle microtubule assembly (ASPM). For validation, we performed a survival analysis using GEPIA against the TCGA database, all four hub genes were upregulated in carcinoma cases compared to normal cases. These four biomarkers found can be used as potential therapeutic targets and as molecular signatures for early detection of NPC.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"43 ","pages":"Article 201376"},"PeriodicalIF":0.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}