Gene最新文献

{"title":"Identification of quantitative trait loci for abdominal muscle content in red swamp crayfish (Procambarus clarkii) and potential application in molecular breeding","authors":"Sun Junxiao ,&nbsp;Bo Peng ,&nbsp;Tan Yunfei ,&nbsp;Bai Xufeng","doi":"10.1016/j.gene.2025.149528","DOIUrl":"10.1016/j.gene.2025.149528","url":null,"abstract":"<div><div>Red swamp crayfish (<em>Procambarus clarkii</em>) is a prized aquatic product among consumers, abdominal muscle content being a crucial economic trait. Therefore, there is an urgent need to exploit the genetic basis of crayfish abdominal muscle content for breeding. In the present study, Quantitative Trait Locus (QTL) mapping was performed using 10 different populations (Pop1–Pop10), raised in water tanks, ponds, and rice-crayfish fields, using single- and multiple-culture models of full-sib families and natural populations, from 2020 to 2023. In total, 22 QTLs for abdominal muscle content were identified with population repetitions, explaining the phenotypic variation in the range of 2.7 %–21.3 %, six of which were heterosis sites. Additionally, nine of the 22 QTLs had the consistent genotype with phenotypic effect in eight natural populations (Pop3–Pop10), where the proportion of genotypes with phenotypic effect of the QTL for abdominal muscle weight / body weight (MW/BW) and chelae weight / body weight (CHW/BW) in the group including the top 10 % of the yield of abdominal muscle content individuals (High group) was significantly higher than that in the group including the bottom 10 % of the yield of abdominal muscle content individuals (Low group), respectively (<em>P</em> &lt; 0.01). These results suggest that the QTLs identified repeatedly, especially the nine QTLs, are reliable candidate loci for abdominal muscle content, which is immensely important for the genetic analysis of abdominal muscle content in red swamp crayfish and molecular marker-assisted breeding.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"959 ","pages":"Article 149528"},"PeriodicalIF":2.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of intronic variants (Apal and Bsml) of vitamin D receptor gene with uterine leiomyoma among North Indian women","authors":"Sonal Tiwari ,&nbsp;Rakesh K. Gupta ,&nbsp;Sakshi Agarwal ,&nbsp;Amita Diwakar ,&nbsp;Arun K. Bind ,&nbsp;Pawan K. Dubey","doi":"10.1016/j.gene.2025.149519","DOIUrl":"10.1016/j.gene.2025.149519","url":null,"abstract":"<div><h3>Background</h3><div>Understanding the genetic factors involved in the Uterine Leiomyoma (UL) development is crucial for exploring the complexities of UL disorders. This study aimed to examine genetic association between UL incidence and intronic polymorphisms of vitamin D receptor gene in north Indian population<em>.</em></div></div><div><h3>Methodology</h3><div>Total 200 subjects (100 healthy women and 100 with uterine leiomyomas) of age- and gender-matched control subjects, were genotyped for BsmI (rs1544410) and ApaI (rs7975232) polymorphisms in the VDR gene using TETRA ARMS PCR, followed by Sanger sequencing validation. Levels of VDR mRNA and vitamin D were also assessed through quantitative real-time PCR and ELISA respectively. The association of these variants with leiomyomas was analyzed, along with clinico-pathological (obesity) association.</div></div><div><h3>Results</h3><div><em>ApaI</em> revealed a significant association with UL, especially for the TG genotype (OR = 2.38; 95 % CI, 1.26–––4.51; <em>p</em> = 0.003). In a similar manner, <em>ApaI</em> is associated with an increased risk for UL with all three genetic models. Comparing VDR ApaI polymorphism between obese and non-obese patients revealed that AC genotype was significantly (OR = 3.71; 95 % CI, 1.53––9.11; <em>p</em> = 0.002) associated with a reduced risk of UL in non-obese patients. The expression of VDR mRNA was two times lower in patients with UL (<em>p</em> &lt; 0.001), along with decreased serum vitamin D levels (<em>p</em> &lt; 0.001). A significant association was also observed between VDR <em>ApaI</em> variant with reduced mRNA expression, vitamin D level and obesity. However, no associations were observed among<!--> <em>Bsm1</em> <!-->VDR genotypes and ULs.</div></div><div><h3>Conclusion</h3><div>This study found significant association between the VDR intronic ApaI polymorphism (rs7975232) and the incidence of UL. This VDR variant showed significant association with reduced VDR mRNA expression and serum vitamin D levels in UL patients. However, no significant association was observed between BsmI VDR polymorphism (rs1544410) and UL in North Indian women.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"959 ","pages":"Article 149519"},"PeriodicalIF":2.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the functional and prognostic roles of EPHX4 in pancreatic cancer: Insights from bioinformatics and experimental validation","authors":"Shaoyang Huang ,&nbsp;Dandan Gu ,&nbsp;Wei Xiong","doi":"10.1016/j.gene.2025.149504","DOIUrl":"10.1016/j.gene.2025.149504","url":null,"abstract":"<div><h3>Background</h3><div>Epoxide hydrolase-4 (EPHX4) belongs to the epoxide hydrolase enzyme family, but its biological function remains unclear, especially its potential involvement in the development of pancreatic tumours. This research sought to examine the function of EPHX4 in pancreatic adenocarcinoma (PAAD).</div></div><div><h3>Methods</h3><div>The expression of EPHX4 across cancers was examined through The Cancer Genome Atlas (TCGA). Bioinformatics was employed, leveraging multiple databases to investigate EPHX4 gene expression in pancreatic cancer and its association with survival prognosis, functional enrichment, immune infiltration, tumour mutation load, and drug sensitivity, among other variables. To evaluate EPHX4 expression in PAAD cells, Western blotting and reverse transcription quantitative PCR were used. A series of <em>in vitro</em> functional experiments was performed to assess the proliferation, migration, and invasion of PAAD cells.</div></div><div><h3>Results</h3><div>EPHX4 expression was markedly elevated in a number of malignancies, including PAAD, and was associated with patient sex, clinical stage, and metastasis to the lymph nodes. High EPHX4 expression was significantly associated with a worse outcome in PAAD patients. According to functional and enrichment studies, EPHX4 is involved in many signalling pathways linked to cancer. The study of immune infiltration revealed that EPHX4 was connected to the existence of a variety of immune cells inside the tumour. Our study revealed that EPHX4 knockdown significantly decreased PAAD cell migration, proliferation, and invasion.</div></div><div><h3>Conclusion</h3><div>EPHX4 is highly expressed in PAAD and independently predicts poor survival. Functional experiments demonstrate its tumor-promoting effects. Its involvement in multiple cancer-related signaling pathways and immune regulation mechanisms highlights the dual prognostic and therapeutic potential of EPHX4 in PAAD.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"959 ","pages":"Article 149504"},"PeriodicalIF":2.6,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperglycaemia-induced fibrotic and inflammatory gene expression alterations in lung epithelial cells: Implications for pulmonary fibrosis development","authors":"Priya Bhardwaj,&nbsp;Mulaka Maruthi","doi":"10.1016/j.gene.2025.149520","DOIUrl":"10.1016/j.gene.2025.149520","url":null,"abstract":"<div><div>Hyperglycaemia has a significant long-term impact on multiple organ systems, including renal, cardiovascular, central nervous, hepatic and ocular systems, leading to the gradual loss of their functional abilities. Numerous studies have elucidated the pathophysiology, etiology, and consequences of hyperglycaemia on these organs. The pulmonary system is also considered as a target of hyperglycaemia, several factors cause lung injury which leads to the development of pulmonary fibrosis, a chronic fibrotic disease with usual interstitial pneumonia patterns. Nevertheless, the effects of hyperglycaemia on the development of pulmonary fibrosis remain poorly understood. We intend to understand the cellular and morphological changes, and the progression of fibrosis in lung epithelial cells subjected to hyperglycaemia. Our experimental data indicate that hyperglycaemia induces fibrotic and inflammatory alterations in cultured lung epithelial cells. These alterations are facilitated by the upregulation of genes related to fibrosis and inflammation, promoting cell proliferation and migration. Further research is required to comprehensively elucidate the impact of hyperglycaemia during lung injury progression of fibrosis, these findings may reveal novel mechanisms that may help in the assessment and treatment of lung ailments in people with hyperglycaemia.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"959 ","pages":"Article 149520"},"PeriodicalIF":2.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA methylation: A new perspective in osteoarthritis research","authors":"Guihao Zheng ,&nbsp;Meifeng Lu ,&nbsp;Yulong Ouyang ,&nbsp;Guicai Sun","doi":"10.1016/j.gene.2025.149518","DOIUrl":"10.1016/j.gene.2025.149518","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by cartilage degradation, osteophyte formation, and joint dysfunction, significantly impairing the quality of life in the elderly population. Recently, RNA modifications, as a dynamic and reversible epigenetic modification, have emerged as critical players in the onset and progression of OA. This review systematically summarizes the major types of RNA modifications involved in OA, including N6-methyladenosine (m6A), 5-methylcytosine (m5C), and 7-methylguanosine (m7G), and explores their roles in regulating chondrocyte autophagy, inflammatory responses, and key signaling pathways. with a primary focus on RNA methylation. Special emphasis is placed on the dynamic regulatory functions of key methyltransferases (e.g., METTL3, FTO, WTAP) and their potential contributions to OA pathogenesis. Furthermore, we address current research hotspots and controversies in the field, proposing future research directions, such as leveraging single-cell sequencing to decipher dynamic RNA modification changes during OA progression and uncovering the cooperative networks among various RNA modifications. Advancing our understanding of the biological roles and mechanisms of RNA modifications holds promise for innovative strategies in the early diagnosis, disease stratification, and targeted therapy of OA.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"959 ","pages":"Article 149518"},"PeriodicalIF":2.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of key regulatory factors in apoptosis of granulosa cells in healthy and atretic pig follicles based on RNA-seq","authors":"Rong Jiang ,&nbsp;Jingjing Su ,&nbsp;Linjie Xu ,&nbsp;Lilian Yang ,&nbsp;Shiyan Sui","doi":"10.1016/j.gene.2025.149514","DOIUrl":"10.1016/j.gene.2025.149514","url":null,"abstract":"<div><div>The molecular mechanism underlying abnormal follicular atresia remains to be elucidated. Research conducted to date has indicated that ovarian granulosa cell (GC) apoptosis is a significant contributor to follicular atresia. Abnormalities in follicular atresia can result in decreased reproductive efficiency in pigs. It is evident that comparative studies focusing on healthy, early atresia and progressively atresia follicles, particularly from the perspective of follicular atresia induced by ovarian GC apoptosis, have not yet been reported. Specifically, the use of RNA-seq technology to systematically analyse differentially expressed genes and associated signaling pathways in GCs at different stages of atresia remains unexplored. The research was divided into three distinct groups: control, early atresia, and progressively atresia. Key genes and signaling pathways were elucidated through RNA-seq. A Venn diagram revealed 86 overlapping genes that were upregulated during early atresia and downregulated during progressively atresia. Additionally, another 47 overlapping genes were found to be downregulated during early atresia and upregulated during progressively atresia. These 133 overlapping genes were significantly enriched in multiple KEGG pathways. Additionally, in conjunction with the key gene-related network diagram, 6 signaling pathways related to ovarian GC apoptosis were further screened out. These pathways include ovarian steroidogenesis, progesterone-mediated oocyte maturation, gonadotropin-releasing hormone signaling pathway, RIG-I-like receptor signaling pathway, NOD-like receptor signaling pathway, and chemokine signaling pathway. Altogether, 12 key genes were identified: SCARB1, IGF1, PRKACA, ADCY6, LDLR, PLD1, CXCL10, IRF7, ISG15, RNase L, OAS2, and STAT1. Six of these genes were randomly selected for qRT-PCR verification, and their expression levels were found to be consistent with the sequencing results. Consequently, the identification of key regulatory factors involved in the apoptotic process provides a theoretical foundation for investigating the mechanisms underlying abnormal follicular atresia in pigs.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"959 ","pages":"Article 149514"},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular identification of F1 hybrids of Fraxinus mandshurica × Fraxinus chinensis using SSR markers","authors":"Xiaonuo Liu ,&nbsp;Huiyuan Xing ,&nbsp;Fanqiu Kong ,&nbsp;Kaifang Zhang ,&nbsp;Yuan Cao ,&nbsp;Xinyue Guo ,&nbsp;Qing Li ,&nbsp;Jingxuan Wang ,&nbsp;Tianzhong Jing ,&nbsp;Yaguang Zhan ,&nbsp;Fenghui Qi","doi":"10.1016/j.gene.2025.149507","DOIUrl":"10.1016/j.gene.2025.149507","url":null,"abstract":"<div><div>To breed new <em>Fraxinus</em> varieties with superior traits including rapid growth, drought tolerance, and salinity resistance, this study established 480 F₁ interspecific hybrid progeny through controlled pollination, using <em>Fraxinus mandshurica</em> Rupr. as the female parent and <em>Fraxinus chinensis</em> Roxb. as the male parent. Early-stage hybrid identification was performed using SSR (simple sequence repeat) markers. From 37 candidate SSR primers, two highly polymorphic pairs were selected for hybrid verification via polyacrylamide gel electrophoresis. Of the 480 offspring, 280 were confirmed as true hybrids, yielding a hybrid purity of 58.33 %. Primer pair Fm19 detected 62.29 % of hybrids, with partial overlap (shared detection) with primer pair Fc1. The polymorphism information content (PIC) ranged from 0.93 to 0.97 (mean: 0.95). Polymorphic alleles from both primers were converted into binary data (1 = present, 0 = absent) to generate unique molecular IDs for 144 hybrid offspring. This work established an efficient SSR-based method for early hybrid identification in <em>F. mandshurica</em> and <em>F. chinensis</em>, facilitating accelerated breeding and variety development.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"959 ","pages":"Article 149507"},"PeriodicalIF":2.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling transposon-mediated multidrug resistance in OXA-23-producing Acinetobacter baumannii ST79/ST233 subclone KL9-OCL10 in Brazil","authors":"João Pedro Rueda Furlan ,&nbsp;Micaela Santana Ramos ,&nbsp;Rafael da Silva Rosa ,&nbsp;Lucas David Rodrigues dos Santos ,&nbsp;Eduardo Angelino Savazzi ,&nbsp;Eliana Guedes Stehling","doi":"10.1016/j.gene.2025.149489","DOIUrl":"10.1016/j.gene.2025.149489","url":null,"abstract":"<div><div>The global dissemination of antimicrobial resistance (AMR) is a critical public health concern. The persistence of AMR in the environmental sector, exemplified by carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB), underscores the critical interconnectedness between human activity, environmental contamination, and the global spread of multidrug-resistant bacterial pathogens. In this study, <em>A. baumannii</em> strain EW779 was isolated from a water sample from a stream impacted by anthropogenic activities in São Paulo State, Brazil, exhibited an extensive drug resistance profile, and harbored chromosome-borne <em>bla</em>_OXA-23 gene. Genomic analysis revealed that EW779 belongs to the hospital-associated high-risk ST79/ST233 subclone KL9-OCL10. This strain harbored a wide resistome associated with mobile genetic elements such as Tn<em>2008</em>, Tn<em>7</em>::In<em>2-4</em>, and Tn<em>3</em>. Virulence genes mainly related to biofilm formation, immune evasion, and cell invasion were found, evidencing its pathogenicity as putative hypervirulent. Comparative genomic analysis revealed that many AMR and virulence traits were shared among ST79/ST233 subclone KL9-OCL10 circulating in Brazil, indicating the occurrence of a successful and potentially epidemic subclone capable of spreading across different regions. The analysis of single nucleotide polymorphism differences among all ST79/ST233 subclone KL9-OCL10 showed a genetic similarity among strains from the same Brazilian state, indicating geographic separation. These findings highlight the environmental persistence and dissemination of a hospital-associated high-risk CRAB clone, emphasizing their epidemiological importance. Therefore, this study contributes to understanding the genomic dynamics of ST79/ST233 subclone KL9-OCL10 and reinforces the need for monitoring the spread of CRAB strains across clinical and environmental settings.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"958 ","pages":"Article 149489"},"PeriodicalIF":2.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forkhead Box M1 isoform 3 overexpression is associated with malignancy grade in adult-type diffuse gliomas","authors":"Iris Angélica Feria-Romero ,&nbsp;Bárbara Nettel-Rueda ,&nbsp;Marco Antonio Rodríguez-Florido ,&nbsp;Guillermo Castellanos-Pallares ,&nbsp;Jesús Cienfuegos-Meza ,&nbsp;Sandra Orozco-Suárez ,&nbsp;Gerardo Guinto-Balanzar ,&nbsp;Consuelo Escamilla-Nuñez ,&nbsp;Israel Grijalva-Otero","doi":"10.1016/j.gene.2025.149502","DOIUrl":"10.1016/j.gene.2025.149502","url":null,"abstract":"<div><h3>Background</h3><div><em>Forkhead Box M1</em> is a transcription factor that is overexpressed in both its mRNA and its protein in various types of cancer. The active <em>Forkhead Box M1 isoform 3 (FOXM1*3)</em> is, moreover, associated with cancer progression. However, little is known about the role of this isoform concerning the degree of malignancy in brain gliomas. This study evaluated the association between overexpression of the <em>FOXM1*3</em> and the degree of malignancy in adult-type diffuse gliomas (ATDGs).</div></div><div><h3>Methods</h3><div>We conducted a prospective study involving 81 samples from patients with ATDGs and ten samples from healthy control cortices. Quantification of the FOXM1*3 transcript and the housekeeping gene, importin 8 (<em>IPO8</em>), was performed using qPCR with Taqman probes. Tumor samples were classified based on their degree of malignancy and cell lineage. Progression-free survival (PFS) was observed through long-term follow-up. The data were then analyzed using the Kruskal-Wallis, Mann-Whitney U and log-rank (Mantel-Cox) tests.</div></div><div><h3>Results</h3><div>The most frequent type of cell differentiation was astrocytic, with astrocytomas and glioblastomas accounting for 80.2 % of cases. The primary histopathological-molecular diagnosis group was glioblastoma, at 35.8 %. There was a significant difference in <em>FOXM1*3</em> expression between the control and glioma groups (p &lt; 0.001). Transcript expression showed significant differences among grade-2, −3, and −4 gliomas (p &lt; 0.005–0.0001). Significant differences were also detected between grade-2 and −3 astrocytomas (p &lt; 0.005) and glioblastomas (p &lt; 0.0001), but not between astrocytomas and oligodendrogliomas of the same grade.</div></div><div><h3>Conclusion</h3><div>We observed that overexpression of <em>FOXM1*3</em> can rectify intra-observer discordance in determining the malignancy grade of gliomas, particularly in grade 3. It can be considered a supplementary tool.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"958 ","pages":"Article 149502"},"PeriodicalIF":2.6,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PD-L1 Promoter Methylation Predicts Gene And Protein Expression Levels in Urothelial Carcinoma","authors":"Cansu Barış Moğul ,&nbsp;Mesut Berkan Duran ,&nbsp;Vildan Caner ,&nbsp;Nilay Şen Türk ,&nbsp;Ömer Levent Tuncay","doi":"10.1016/j.gene.2025.149503","DOIUrl":"10.1016/j.gene.2025.149503","url":null,"abstract":"<div><div>We aimed to clarify the role of <em>PD-L1</em> promoter methylation in bladder cancer by analyzing <em>PD-L1</em> methylation and mRNA expression in FFPE samples, along with PD-L1 mRNA and protein levels in urine samples from bladder urothelial carcinoma patients.</div><div>We analyzed <em>PD-L1</em> promoter methylation in 43 bladder urothelial carcinoma tissue samples and 41 non-malignant bladder tissues using methylation-sensitive high-resolution melting analysis to assess two CpG islands (cg15837913, cg19724470). PD-L1 mRNA expression in tissues and urine samples, along with PD-L1 protein levels in urine, were evaluated.</div><div>The bladder urothelial carcinoma group showed significantly higher methylation rates for cg19724470 and cg15837913 compared to controls (<em>P</em> = 0.016, <em>P</em> = 0.049 respectively). In the patient group, tissue <em>PD-L1</em> mRNA expression was 15.22 times higher and urinary <em>PD-L1</em> mRNA expression 6.56 times higher in the cg19724470 unmethylated group compared to the methylated group. Urinary PD-L1 protein concentration was twice as high in the cg19724470 unmethylated group compared to the methylated group. In the patients, tissue PD-L1 mRNA expression was 4.58 times higher and urinary PD-L1 mRNA expression 2.58 times higher in the cg15837913 unmethylated group compared to the methylated group. Moreover, the urinary PD-L1 protein concentration was 1.7 times higher in the cg15837913 unmethylated group than in the methylated group (<em>P</em> = 0.036). A positive correlation was observed between tissue <em>PD-L1</em> mRNA and both urine PD-L1 mRNA and protein levels and between urine <em>PD-L1</em> mRNA and protein levels.</div><div>This study suggests that <em>PD-L1</em> methylation may be a key epigenetic regulator influencing <em>PD-L1</em> expression and disease pathogenesis in bladder urothelial carcinoma.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"959 ","pages":"Article 149503"},"PeriodicalIF":2.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}