Pub Date : 2025-11-25DOI: 10.1016/j.gene.2025.149919
Carlotta Frascolla , Riccardo Mastroianni , Giuseppe Simone , Giovanni Blandino
Bladder cancer (BCa) remains one of the most challenging malignancies in oncology, driven by deep molecular heterogeneity, dynamic tumor evolution and complex tumor–microenvironment interactions. Despite advances in molecular characterization and the introduction of new treatments, translating biological knowledge into meaningful clinical benefits remains a major bottleneck. In recent years, next-generation 3D preclinical models have emerged as essential tools to recapitulate BCa complexity, offering new opportunities to investigate tumor biology and support the development of personalized treatment strategies. This review provides an overview of available 3D models for BCa, discusses their application and highlights their growing integration into clinical trials to guide real-time therapeutic decisions.
{"title":"The role of 3D preclinical models in the Era of precision medicine: A bladder cancer perspective","authors":"Carlotta Frascolla , Riccardo Mastroianni , Giuseppe Simone , Giovanni Blandino","doi":"10.1016/j.gene.2025.149919","DOIUrl":"10.1016/j.gene.2025.149919","url":null,"abstract":"<div><div>Bladder cancer (BCa) remains one of the most challenging malignancies in oncology, driven by deep molecular heterogeneity, dynamic tumor evolution and complex tumor–microenvironment interactions. Despite advances in molecular characterization and the introduction of new treatments, translating biological knowledge into meaningful clinical benefits remains a major bottleneck. In recent years, next-generation 3D preclinical models have emerged as essential tools to recapitulate BCa complexity, offering new opportunities to investigate tumor biology and support the development of personalized treatment strategies. This review provides an overview of available 3D models for BCa, discusses their application and highlights their growing integration into clinical trials to guide real-time therapeutic decisions.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149919"},"PeriodicalIF":2.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616554","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}
Pub Date : 2025-11-23DOI: 10.1016/j.gene.2025.149917
Yunyi Liu, Peiyun Zhuang
Laryngeal leukoplakia represents the most frequent precancerous lesion in laryngeal carcinogenesis, yet its transformation mechanisms remain elusive. By performing scRNA-seq on ten clinical specimens (five leukoplakia lesions across pathological stages, four early carcinomas, and one control), we established the first single-cell atlas of this malignant progression. Computational analysis revealed dynamic microenvironmental shifts dominated by epithelial cells, fibroblasts, and mononuclear phagocytes. We identified two critical epithelial subpopulations: Epi_4 (tumor-like cells), a high-grade dysplasia-specific subpopulation with high malignant potential, and Epi_5 (tumor cells) in carcinoma, which carries a favorable prognostic gene signature (Module 3). Furthermore, Epi_4 showed preferential communication with cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) via the JAG1-NOTCH4 and CXCL5-CXCR1 axes, suggesting actionable therapeutic targets. We also observed the progressive activation of genes involved in redox processes (NQO1, GSTM3, UCHL1, NTRK2) via the KEAP1-NRF2 pathway. This work systematically characterizes the cellular and molecular landscape during laryngeal leukoplakia malignant transformation, providing a framework for future mechanistic studies and early detection strategies.
{"title":"Dynamic tumor microenvironment remodeling from laryngeal leukoplakia to carcinoma revealed by single-cell transcriptomics","authors":"Yunyi Liu, Peiyun Zhuang","doi":"10.1016/j.gene.2025.149917","DOIUrl":"10.1016/j.gene.2025.149917","url":null,"abstract":"<div><div>Laryngeal leukoplakia represents the most frequent precancerous lesion in laryngeal carcinogenesis, yet its transformation mechanisms remain elusive. By performing scRNA-seq on ten clinical specimens (five leukoplakia lesions across pathological stages, four early carcinomas, and one control), we established the first single-cell atlas of this malignant progression. Computational analysis revealed dynamic microenvironmental shifts dominated by epithelial cells, fibroblasts, and mononuclear phagocytes. We identified two critical epithelial subpopulations: Epi_4 (tumor-like cells), a high-grade dysplasia-specific subpopulation with high malignant potential, and Epi_5 (tumor cells) in carcinoma, which carries a favorable prognostic gene signature (Module 3). Furthermore, Epi_4 showed preferential communication with cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) via the JAG1-NOTCH4 and CXCL5-CXCR1 axes, suggesting actionable therapeutic targets. We also observed the progressive activation of genes involved in redox processes (NQO1, GSTM3, UCHL1, NTRK2) via the KEAP1-NRF2 pathway. This work systematically characterizes the cellular and molecular landscape during laryngeal leukoplakia malignant transformation, providing a framework for future mechanistic studies and early detection strategies.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149917"},"PeriodicalIF":2.4,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603115","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}
Pub Date : 2025-11-23DOI: 10.1016/j.gene.2025.149916
Marcelo Arancibia , Jefferson Rojas , M. Leonor Bustamante
Advances in genetics and genomics have transformed our understanding of personality. The observation that personality traits run in families has prompted extensive study into their heritability and underlying genetic architecture. However, there is a significant discrepancy between psychiatric classifications of personality disorders and genomic findings, suggesting a need to reorient these classifications toward a more dimensional, biologically informed perspective. This article reviews key genetic and genomic findings in personality, focusing on the “Big Five” model, which has proven consistency with genomic research. Twin studies estimate heritability accounts for about 40–50 % of personality traits, while the rest of phenotypic variation is explained by the non-shared environment, which influence personality through epigenetic changes. Genome-wide association studies (GWAS) have identified numerous genetic variants on nearly all chromosomes that influence personality traits, particularly neuroticism. These variants are involved in biological pathways such as neurogenesis and neuronal differentiation. GWAS have also revealed significant genetic correlations between personality traits and major psychiatric disorders, supporting a biological continuum between them. This supports the hypothesis which states that a typical behavioral trait is associated with many genetic variants, each contributing a very small effect. Future research should incorporate epigenetic evidence, study genetic interactions, and expand the diversity of study populations beyond European ancestry to improve the generalizability of findings.
{"title":"Heredity and personality: A review of concepts, methods, and evidence","authors":"Marcelo Arancibia , Jefferson Rojas , M. Leonor Bustamante","doi":"10.1016/j.gene.2025.149916","DOIUrl":"10.1016/j.gene.2025.149916","url":null,"abstract":"<div><div>Advances in genetics and genomics have transformed our understanding of personality. The observation that personality traits run in families has prompted extensive study into their heritability and underlying genetic architecture. However, there is a significant discrepancy between psychiatric classifications of personality disorders and genomic findings, suggesting a need to reorient these classifications toward a more dimensional, biologically informed perspective. This article reviews key genetic and genomic findings in personality, focusing on the “Big Five” model, which has proven consistency with genomic research. Twin studies estimate heritability accounts for about 40–50 % of personality traits, while the rest of phenotypic variation is explained by the non-shared environment, which influence personality through epigenetic changes. Genome-wide association studies (GWAS) have identified numerous genetic variants on nearly all chromosomes that influence personality traits, particularly neuroticism. These variants are involved in biological pathways such as neurogenesis and neuronal differentiation. GWAS have also revealed significant genetic correlations between personality traits and major psychiatric disorders, supporting a biological continuum between them. This supports the hypothesis which states that a typical behavioral trait is associated with many genetic variants, each contributing a very small effect. Future research should incorporate epigenetic evidence, study genetic interactions, and expand the diversity of study populations beyond European ancestry to improve the generalizability of findings.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149916"},"PeriodicalIF":2.4,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603455","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}
Pub Date : 2025-11-20DOI: 10.1016/j.gene.2025.149915
Youmei Wu, Xinzhu Li, Junyang Chen, Bo Yang, Xiaojun Yang, Jin Hou
Tooth agenesis (TA), one of the most common craniofacial developmental anomalies, is characterized by the congenital absence of one or more teeth. While numerous genes have been implicated in non-syndromic tooth agenesis (NSTA), its genetic architecture often remains complex. In this study, we investigated the genetic basis of NSTA in a two-generation Chinese family utilizing whole-exome sequencing (WES) complemented by Sanger sequencing. Our analysis revealed a complex segregation pattern of multiple variants. After systematic filtering based on pathogenicity predictions and minor allele frequency (MAF), we identified eight potential contributory variants. These include homozygous missense variants in EDAR (c.1109 T > C), GHR (c.1630A > C), and COL17A1 (c.629C > T), a heterozygous missense variant in CEP152 (c.161C > T), and DSP (c.5213G > A) and three rare heterozygous missense variants in CCDC154 (c.925C > T), FRAS1 (c.9628G > A), and NBAS (c.5095G > A). Notably, the variants in GHR, CCDC154, FRAS1, and NBAS represent potential novel candidate genes for NSTA, thereby expanding the variant spectrum associated with this condition. The co-segregation of these multi-locus variants suggests that inheritance might be complex, perhaps involving oligogenic mechanisms. This points to the possibility of intricate genetic interactions in tooth development, offering new clues about the molecular basis of familial NSTA.
{"title":"Genetic analysis of a Chinese family with non-syndromic tooth agenesis may reveal a potential multi-locus etiology","authors":"Youmei Wu, Xinzhu Li, Junyang Chen, Bo Yang, Xiaojun Yang, Jin Hou","doi":"10.1016/j.gene.2025.149915","DOIUrl":"10.1016/j.gene.2025.149915","url":null,"abstract":"<div><div>Tooth agenesis (TA), one of the most common craniofacial developmental anomalies, is characterized by the congenital absence of one or more teeth. While numerous genes have been implicated in non-syndromic tooth agenesis (NSTA), its genetic architecture often remains complex. In this study, we investigated the genetic basis of NSTA in a two-generation Chinese family utilizing whole-exome sequencing (WES) complemented by Sanger sequencing. Our analysis revealed a complex segregation pattern of multiple variants. After systematic filtering based on pathogenicity predictions and minor allele frequency (MAF), we identified eight potential contributory variants. These include homozygous missense variants in <em>EDAR</em> (c.1109 T > C), <em>GHR</em> (c.1630A > C), and <em>COL17A1</em> (c.629C > T), a heterozygous missense variant in <em>CEP152</em> (c.161C > T), and <em>DSP</em> (c.5213G > A) and three rare heterozygous missense variants in <em>CCDC154</em> (c.925C > T), <em>FRAS1</em> (c.9628G > A), and <em>NBAS</em> (c.5095G > A). Notably, the variants in <em>GHR</em>, <em>CCDC154</em>, <em>FRAS1</em>, and <em>NBAS</em> represent potential novel candidate genes for NSTA, thereby expanding the variant spectrum associated with this condition. The co-segregation of these multi-locus variants suggests that inheritance<!--> <!-->might<!--> <!-->be complex, perhaps involving oligogenic mechanisms. This<!--> <!-->points to the possibility<!--> <!-->of intricate genetic interactions in tooth development, offering new clues about the molecular basis of familial NSTA.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"979 ","pages":"Article 149915"},"PeriodicalIF":2.4,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582018","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}
Pub Date : 2025-11-20DOI: 10.1016/j.gene.2025.149910
Lilian de Sá Garcia Landeiro , Pedro Augusto Silva dos Santos Rodrigues , Almirane Lima de Oliveira , Katarina Mattos Brandão , Laryssa Cardoso Calmon , João Victor Andrade Cruz , Mailane dos Anjos Silva , Bruna Ramos Tosta , Ingrid de Marins de Almeida , João Locke Ferreira de Araújo , Thamara Miranda Barbosa dos Santos , Milca de Jesus Silva , Gabriela Pimentel Pinheiro das Chagas , Álvaro Augusto Souza da Cruz Filho , Camila Alexandrina Viana de Figueirêdo , Pablo de Moura Santos , Ryan dos Santos Costa
Objective
Rheumatoid arthritis (RA) is a chronic inflammatory disease that can lead to progressive disability. TNF inhibitors (TNFi) have shown promise in improving disease progression and prognosis; however, only 60% to 70% of patients respond well. Genetic variations have been linked to this therapeutic failure. Genetic variants in the IL17 gene are associated with TNFi therapy responses and RA susceptibility, but few studies have explored this in the Brazilian population. This study assesses variants in the IL-17 pathway (rs763780, rs2275913, rs3819024) in RA patients undergoing TNFi treatment in Salvador, BA. Methods: A total of 497 individuals (294 RA patients, 203 healthy controls) were included. Plasma levels of IL-17, IL-1β, TNF, and other cytokines were measured in a subpopulation. Meta-analysis of published studies was conducted to consolidate associations between IL and 17 variants and RA susceptibility. Results: No significant associations were found between SNVs and RA susceptibility in the cohort, while the meta-analysis revealed protective and risk associations. The rs3819024-G allele was associated with improved TNFi response, particularly in infliximab users, whereas rs2275913-AA carriers had higher risk of treatment.
{"title":"IL17 genetic variants impact the response and safety of TNFi treatment in rheumatoid arthritis patients from Bahia, Brazil","authors":"Lilian de Sá Garcia Landeiro , Pedro Augusto Silva dos Santos Rodrigues , Almirane Lima de Oliveira , Katarina Mattos Brandão , Laryssa Cardoso Calmon , João Victor Andrade Cruz , Mailane dos Anjos Silva , Bruna Ramos Tosta , Ingrid de Marins de Almeida , João Locke Ferreira de Araújo , Thamara Miranda Barbosa dos Santos , Milca de Jesus Silva , Gabriela Pimentel Pinheiro das Chagas , Álvaro Augusto Souza da Cruz Filho , Camila Alexandrina Viana de Figueirêdo , Pablo de Moura Santos , Ryan dos Santos Costa","doi":"10.1016/j.gene.2025.149910","DOIUrl":"10.1016/j.gene.2025.149910","url":null,"abstract":"<div><h3>Objective</h3><div>Rheumatoid arthritis (RA) is a chronic inflammatory disease that can lead to progressive disability. TNF inhibitors (TNFi) have shown promise in improving disease progression and prognosis; however, only 60% to 70% of patients respond well. Genetic variations have been linked to this therapeutic failure. Genetic variants in the IL17 gene are associated with TNFi therapy responses and RA susceptibility, but few studies have explored this in the Brazilian population. This study assesses variants in the IL-17 pathway (rs763780, rs2275913, rs3819024) in RA patients undergoing TNFi treatment in Salvador, BA. Methods: A total of 497 individuals (294 RA patients, 203 healthy controls) were included. Plasma levels of IL-17, IL-1β, TNF, and other cytokines were measured in a subpopulation. Meta-analysis of published studies was conducted to consolidate associations between IL and 17 variants and RA susceptibility. Results: No significant associations were found between SNVs and RA susceptibility in the cohort, while the <em>meta</em>-analysis revealed protective and risk associations. The rs3819024-G allele was associated with improved TNFi response, particularly in infliximab users, whereas rs2275913-AA carriers had higher risk of treatment.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149910"},"PeriodicalIF":2.4,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577705","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}
Pub Date : 2025-11-20DOI: 10.1016/j.gene.2025.149914
Yunwei Zhao, Kaifan Shang, Ping Wang
Pugionium cornutum is a biennial herb belonging to the Brassicaceae family and is an endemic species of the Mongolian Plateau, exhibiting strong stress tolerance and notable medicinal value. In this study, the PcHARBI1-5 gene was cloned from P. cornutum and functionally characterized through heterologous transformation in Arabidopsis thaliana. Transgenic overexpression lines (OE) and homologous knockout mutants (KO-1) were generated, and their phenotypic differences were systematically evaluated under controlled conditions. Overexpression of PcHARBI1-5 significantly promoted early flowering in Arabidopsis, with transgenic plants flowering approximately four days earlier than wild-type controls, whereas the KO-1 mutant exhibited a delay of about three days. Furthermore, transgenic lines displayed enhanced agronomic performance, including longer roots, increased plant height, greater lateral branching, elongated siliques, and higher seed yield per plant. Gene expression analysis revealed that PcHARBI1-5 modulates flowering time by down-regulating the floral repressor FLC and up-regulating key floral integrators FT and SOC1. Taken together, this study reports the successful cloning and functional validation of PcHARBI1-5 from P. cornutum, demonstrating its pivotal role in accelerating flowering and improving multiple agronomic traits. These findings highlight PcHARBI1-5 as a promising candidate gene for molecular breeding strategies aimed at developing early-maturing and high-yielding crop varieties.
{"title":"Pugionium cornutum PcHARBI1-5 (Harbinger Transposase Derived 1–5) facilitates early flowing and seed development in in Arabidopsis thaliana","authors":"Yunwei Zhao, Kaifan Shang, Ping Wang","doi":"10.1016/j.gene.2025.149914","DOIUrl":"10.1016/j.gene.2025.149914","url":null,"abstract":"<div><div><em>Pugionium cornutum</em> is a biennial herb belonging to the Brassicaceae family and is an endemic species of the Mongolian Plateau, exhibiting strong stress tolerance and notable medicinal value. In this study, the <em>PcHARBI1-5</em> gene was cloned from <em>P. cornutum</em> and functionally characterized through heterologous transformation in <em>Arabidopsis thaliana</em>. Transgenic overexpression lines (OE) and homologous knockout mutants (KO-1) were generated, and their phenotypic differences were systematically evaluated under controlled conditions. Overexpression of <em>PcHARBI1-5</em> significantly promoted early flowering in <em>Arabidopsis</em>, with transgenic plants flowering approximately four days earlier than wild-type controls, whereas the KO-1 mutant exhibited a delay of about three days. Furthermore, transgenic lines displayed enhanced agronomic performance, including longer roots, increased plant height, greater lateral branching, elongated siliques, and higher seed yield per plant. Gene expression analysis revealed that <em>PcHARBI1-5</em> modulates flowering time by down-regulating the floral repressor <em>FLC</em> and up-regulating key floral integrators <em>FT</em> and <em>SOC1</em>. Taken together, this study reports the successful cloning and functional validation of <em>PcHARBI1-5</em> from <em>P. cornutum</em>, demonstrating its pivotal role in accelerating flowering and improving multiple agronomic traits. These findings highlight <em>PcHARBI1-5</em> as a promising candidate gene for molecular breeding strategies aimed at developing early-maturing and high-yielding crop varieties.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149914"},"PeriodicalIF":2.4,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145577704","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}
Pub Date : 2025-11-19DOI: 10.1016/j.gene.2025.149913
Mahamane T. Diakité , Shan Sun , Anou M. Somboro , Brehima Diakité , Amadou Koné , Yaya Kassogué , Djeneba Fofana , Saidou Balam , Cheick B Traoré , Aminata Maiga , Bakarou Kamaté , Djibril Ba , Modibo Diarra , Soungou Boré , Almoustapha I. Maiga , Qi Dai , Drew Robert Nannini , Jane Holl , Robert Murphy , Lifang Hou , Mamoudou Maiga
Aim
To conduct a case-control study (pilot study) in Africa (Mali) in comparing the gut microbiota of patients with stage III colorectal cancer (CRC) using next-generation sequencing.
Methods
Shotgun sequencing was performed to characterize participants’ fecal microbiota using Illumina’s HiSeq platform. This case-control study involved newly diagnosed CRC patients (n = 23) prior to any treatment initiation, and unrelated healthy controls (n = 24) to elucidate their microbial diversity and relative abundance.
Results
The findings revealed that the gut microbiota in CRC and in healthy were significantly distinctive according to the PERMANOVA test (R2 = 0.132, P = 0.001), and the alpha-diversity was significantly lower in CRC. Beta-diversity, based on principal coordinate analysis, showed a distinct taxonomy between the CRC and the healthy.
Levels of Pseudomonadota, Escherichia, Citrobacter freundii, Klebsiella sp. LTGPAF-6F, Escherichia albertii, Escherichia coli, Caudovirales, Apicomplexa, and Verrucomicrobiota populations were significantly elevated in CRC. The major metabolic pathways with higher relative abundance levels found in CRC compared to healthy were related to HEMESYN2-PWY: heme biosynthesis II (anaerobic), PWY-5154:L-arginine biosynthesis III (via N-acetyl-L-citrulline), FUC-RHAMCAT-PWY: superpathway of fucose and rhamnose degradation, ECASYN-PWY: enterobacterial common antigen biosynthesis, ENTBACSYN-PWY: enterobactin biosynthesis, and AEROBACTINSYN-PWY: aerobactin biosynthesis.
Conclusion
Distinct gut microbiome profiles between healthy and CRC were observed. In particular, the findings showed a significant reduction in microbial diversity in stage III CRC. This study provides initial metagenomic data on Malian patients with CRC. It will be used to create a larger cohort to better understand the relationship between CRC and the gut microbiota in the Malian CRC population.
{"title":"Characterization of the gut microbiota in patients with stage III colorectal cancer: A case-control study","authors":"Mahamane T. Diakité , Shan Sun , Anou M. Somboro , Brehima Diakité , Amadou Koné , Yaya Kassogué , Djeneba Fofana , Saidou Balam , Cheick B Traoré , Aminata Maiga , Bakarou Kamaté , Djibril Ba , Modibo Diarra , Soungou Boré , Almoustapha I. Maiga , Qi Dai , Drew Robert Nannini , Jane Holl , Robert Murphy , Lifang Hou , Mamoudou Maiga","doi":"10.1016/j.gene.2025.149913","DOIUrl":"10.1016/j.gene.2025.149913","url":null,"abstract":"<div><h3>Aim</h3><div>To conduct a case-control study (pilot study) in Africa (Mali) in comparing the gut microbiota of patients with stage III colorectal cancer (CRC) using next-generation sequencing.</div></div><div><h3>Methods</h3><div>Shotgun sequencing was performed to characterize participants’ fecal microbiota using Illumina’s HiSeq platform. This case-control study involved newly diagnosed CRC patients (n = 23) prior to any treatment initiation, and unrelated healthy controls (n = 24) to elucidate their microbial diversity and relative abundance.</div></div><div><h3>Results</h3><div>The findings revealed that the gut microbiota in CRC and in healthy were significantly distinctive according to the PERMANOVA test (R<sup>2</sup> = 0.132, P = 0.001), and the alpha-diversity was significantly lower in CRC. Beta-diversity, based on principal coordinate analysis, showed a distinct taxonomy between the CRC and the healthy.</div><div>Levels of <em>Pseudomonadota</em>, <em>Escherichia</em>, <em>Citrobacter freundii</em>, <em>Klebsiella</em> sp. <em>LTGPAF-6F</em>, <em>Escherichia albertii, Escherichia coli, Caudovirales</em>, <em>Apicomplexa,</em> and <em>Verrucomicrobiota</em> populations were significantly elevated in CRC. The major metabolic pathways with higher relative abundance levels found in CRC compared to healthy were related to <em>HEMESYN2-PWY: heme biosynthesis II (anaerobic)</em>, <em>PWY-5154:L-arginine biosynthesis III (via N-acetyl-L-citrulline)</em>, <em>FUC-RHAMCAT-PWY: superpathway of fucose and rhamnose degradation</em>, <em>ECASYN-PWY: enterobacterial common antigen biosynthesis, ENTBACSYN-PWY: enterobactin biosynthesis,</em> and <em>AEROBACTINSYN-PWY: aerobactin biosynthesis.</em></div></div><div><h3>Conclusion</h3><div>Distinct gut microbiome profiles between healthy and CRC were observed. In particular, the findings showed a significant reduction in microbial diversity in stage III CRC. This study provides initial metagenomic data on Malian patients with CRC. It will be used to create a larger cohort to better understand the relationship between CRC and the gut microbiota in the Malian CRC population.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149913"},"PeriodicalIF":2.4,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573420","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}
Pub Date : 2025-11-17DOI: 10.1016/j.gene.2025.149823
Lei Qiao, Yong Feng
{"title":"Retraction notice to “Genetic variations of prostate stem cell antigen (PSCA) contribute to the risk of gastric cancer for Eastern Asians: a Meta-analysis based on 16792 individuals”. [Gene 493 (2012) 83–91]","authors":"Lei Qiao, Yong Feng","doi":"10.1016/j.gene.2025.149823","DOIUrl":"10.1016/j.gene.2025.149823","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"976 ","pages":"Article 149823"},"PeriodicalIF":2.4,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548980","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}
Pub Date : 2025-11-14DOI: 10.1016/j.gene.2025.149902
Juan Zhu , Zi-yan Xu , Hong-ping Yu , Ruo-li Wang , Yi-jia Luo , Li-jun Xie , Jian-hui Zhang , Qian Chen , Peng-fei Wang , Dan-dan Ruan , Jing Zou , Yan-feng Zhou , Li Chen , Fang-meng Huang , Mei-zhu Gao , Li Zhang , Yun-fei Li , Zhu-ting Fang , Li-sheng Liao , Xi-kui Zhang , Zhi-hai Zheng
This study identifies two pedigrees with autosomal dominant polycystic kidney disease (ADPKD) caused by de novo PKD1 variants. Proband A carried a heterozygous splicing variant (c.9202-16G > A), presenting with bilateral renal cysts. The miniGENE assay confirmed this variant causes aberrant splicing with a 60-base excision, leading to a frameshift and a predicted truncated protein. Proband B carried a missense variant (c.2180 T > C; p.Leu727Pro), presenting with polycystic kidney and liver disease. Structural modeling revealed this variant severely disrupts local secondary structure and a critical spatial interaction, compromising protein stability. Functional analyses demonstrate that both de novo variants are pathogenic through distinct mechanisms, implicating aberrant splicing and structural disruption in ADPKD etiology.
本研究确定了两个常染色体显性多囊肾病（ADPKD）的家系，这些多囊肾病是由新的PKD1变异引起的。先证A携带杂合剪接变体（c.9202-16G > A），表现为双侧肾囊肿。miniGENE试验证实，该变异导致60个碱基切除的异常剪接，导致移码和预测的截断蛋白。先证者B携带错义变异（C .2180 T > C; p.Leu727Pro），表现为多囊肾和肝脏疾病。结构模型显示，这种变异严重破坏了局部二级结构和关键的空间相互作用，损害了蛋白质的稳定性。功能分析表明，这两种新生变异通过不同的机制致病，暗示了ADPKD病因中的异常剪接和结构破坏。
{"title":"De novo PKD1 splicing and missense variants in two familial ADPKD: Molecular characterization and genetic counseling implications","authors":"Juan Zhu , Zi-yan Xu , Hong-ping Yu , Ruo-li Wang , Yi-jia Luo , Li-jun Xie , Jian-hui Zhang , Qian Chen , Peng-fei Wang , Dan-dan Ruan , Jing Zou , Yan-feng Zhou , Li Chen , Fang-meng Huang , Mei-zhu Gao , Li Zhang , Yun-fei Li , Zhu-ting Fang , Li-sheng Liao , Xi-kui Zhang , Zhi-hai Zheng","doi":"10.1016/j.gene.2025.149902","DOIUrl":"10.1016/j.gene.2025.149902","url":null,"abstract":"<div><div>This study identifies two pedigrees with autosomal dominant polycystic kidney disease (ADPKD) caused by de novo PKD1 variants. Proband A carried a heterozygous splicing variant (c.9202-16G > A), presenting with bilateral renal cysts. The miniGENE assay confirmed this variant causes aberrant splicing with a 60-base excision, leading to a frameshift and a predicted truncated protein. Proband B carried a missense variant (c.2180 T > C; p.Leu727Pro), presenting with polycystic kidney and liver disease. Structural modeling revealed this variant severely disrupts local secondary structure and a critical spatial interaction, compromising protein stability. Functional analyses demonstrate that both de novo variants are pathogenic through distinct mechanisms, implicating aberrant splicing and structural disruption in ADPKD etiology.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"978 ","pages":"Article 149902"},"PeriodicalIF":2.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534407","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}
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