BMC Medical Genomics最新文献

{"title":"Causal associations between inflammatory bowel disease and sepsis: a two-sample Mendelian randomization study.","authors":"Renyang Tong, Ziting Liang, Chengui Zhuo, Xueyang Bai, Ling Dao, Lu Yu, Ling Li, Zhaohui Tong, Youyou Du, Longwei Xu","doi":"10.1186/s12920-025-02143-2","DOIUrl":"https://doi.org/10.1186/s12920-025-02143-2","url":null,"abstract":"<p><strong>Background: </strong>Recent observational studies have revealed an inconclusive correlation between inflammatory bowel disease (IBD) and sepsis, accompanied by an uncertain understanding of the causal relationship between the two. To investigate the causality between IBD and sepsis, we employed a two-sample Mendelian randomization (MR) approach.</p><p><strong>Methods: </strong>A genome-wide significant threshold (P < 5 × 10^-8) was achieved in order to identify single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for two types of IBD, such as Crohn's disease (CD) and ulcerative colitis (UC). Subsequently, the selected SNPs were assessed in relation to three categories of sepsis, namely sepsis, sepsis (critical care), and sepsis (28-day death in critical care). An inverse-variance weighted (IVW) estimation of MR was conducted, followed by sensitivity analysis on multiple dimensions.</p><p><strong>Results: </strong>There was a significant association between genetic liability to CD (IVW: OR, 1.246; 95% CI, 1.090-1.423; P = 0.0012) with sepsis (28-day death in critical care), but not with sepsis (critical care) and sepsis. Whereas UC showed slightly, yet statistically insignificant, higher risk for sepsis (IVW: OR, 1.031; 95% CI, 0.988-1.064; P = 0.064).</p><p><strong>Conclusion: </strong>Our study offers genetic evidence that supports a substantial causal relationship between CD and sepsis (28-day death in critical care). To enhance the specificity and objectivity of future research findings, it is recommended to specify the types of IBD and the severity of sepsis. Furthermore, the genetic risk loci related may become potential drug development targets.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"74"},"PeriodicalIF":2.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Underrepresented populations in genomic research: a qualitative study of researchers' perspectives.","authors":"Arian Omeranovic, Flora Nguyen Van Long, Asma Boubaker, Annie Turgeon, Hermann Nabi","doi":"10.1186/s12920-025-02140-5","DOIUrl":"https://doi.org/10.1186/s12920-025-02140-5","url":null,"abstract":"<p><strong>Background: </strong>The lack of diversity in genomic data limits researchers' ability to investigate the relationships between genetic profiles, disease manifestations, and responses to new therapies. As a result, innovations in treatment could have potentially harmful effects on a significant portion of the population due to incomplete or inaccurate genomic data. In addition, the lack of harmonization in the use of population descriptors in genomic studies raises both ethical and scientific concerns regarding which descriptors should be used to study and recruit underrepresented populations. Therefore, understanding the factors contributing to the lack of diversity in genomic research is an urgent scientific, clinical, and public health priority. This study aims to explore the social and contextual factors influencing the participation of underrepresented populations in genomic research, from the perspective of researchers in the field.</p><p><strong>Methods: </strong>A total of 13 semi-structured interviews were conducted with researchers experienced in genomic research in Canada and fluent in either French or English. The interview transcripts were analyzed using thematic analysis.</p><p><strong>Results: </strong>Researchers identified several factors contributing to the low participation of underrepresented populations in genomic research, with one key factor being the geographic distribution of research institutions and the disconnect between research efforts and the communities being studied. To address this issue, participants stressed the importance of moving away from colonial practices, such as conducting research on a community without consulting its members in the design phase. Furthermore, it was suggested that existing diversity, equity, and inclusion policies alone were insufficient to effectively address the challenge. Lastly, the study also highlighted a potential link between how study populations are categorized and the willingness of underrepresented groups to participate in genomic research.</p><p><strong>Conclusion: </strong>Although researchers are generally aware of the literature on the causes, consequences, and potential solutions for increasing participation, confusion remains regarding the use of population descriptors. Our findings highlight the need for improved education, greater consensus, and expanded dialogue within the genomic research community to promote the harmonization of population descriptors.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"72"},"PeriodicalIF":2.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease candidate genes prediction using positive labeled and unlabeled instances.","authors":"Sepideh Molaei, Saeed Jalili","doi":"10.1186/s12920-025-02109-4","DOIUrl":"https://doi.org/10.1186/s12920-025-02109-4","url":null,"abstract":"<p><p>Identifying disease genes and understanding their performance is critical in producing drugs for genetic diseases. Nowadays, laboratory approaches are not only used for disease gene identification but also using computational approaches like machine learning are becoming considerable for this purpose. In machine learning methods, researchers can only use two data types (disease genes and unknown genes) to predict disease candidate genes. Notably, there is no source for the negative data set. The proposed method is a two-step process: The first step is the extraction of reliable negative genes from a set of unlabeled genes by one-class learning and a filter based on distance indicators from known disease genes; this step is performed separately for each disease. The second step is the learning of a binary model using causing genes of each disease as a positive learning set and the reliable negative genes extracted from that disease. Each gene in the unlabeled gene's production and ranking step is assigned a normalized score using two filters and a learned model. Consequently, disease genes are predicted and ranked. The proposed method evaluation of various six diseases and Cancer class indicates better results than other studies.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"73"},"PeriodicalIF":2.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12004746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver cancer-specific prognostic model developed using endoplasmic reticulum stress-related LncRNAs and LINC01011 as a potential therapeutic target.","authors":"Xiao Du, Ning Wei, Anqi Wang, Guoping Sun","doi":"10.1186/s12920-025-02142-3","DOIUrl":"https://doi.org/10.1186/s12920-025-02142-3","url":null,"abstract":"<p><p>Liver cancer is a serious malignancy worldwide, and long noncoding RNAs (lncRNAs) have been implicated in its prognosis.It remains unclear how lncRNAs related to endoplasmic reticulum stress (ERS) influence liver cancer prognosis. Here, we analyzed RNA and clinical data from the Cancer Genome Atlas and sourced ERS-related genes from the Molecular Signatures Database. Co-expression analysis identified ERS-related lncRNAs, and Cox regression analysis as well as least absolute shrinkage and selection operator regression highlighted three lncRNAs for a prognostic model. Based on median risk scores, we classified patients into two risk groups. The high-risk group displayed poor prognosis, and this finding was validated in the test set. According to consistency clustering, the patients were assigned to two clusters, and tumor microenvironment scores were computed. Patients with a high mutation burden had worse outcomes. Furthermore, immune infiltration analysis indicated more immune cells and mutations in checkpoint molecules among high-risk individuals. Drug sensitivity varied between the risk groups. LINC01011 was selected for functional assays. Colony formation assay and CCK-8 assay revealed that silencing LINC01011 suppressed liver cancer cell proliferation. Transwell and scratch assays indicated that silencing LINC01011 inhibited liver cancer cell migration. Western blotting assay revealed that inhibiting LINC01011 induced apoptosis and simultaneously inhibited epithelial-mesenchymal transition. These findings confirm the validity of the prognostic model and indicate that LINC01011 could serve as a potential research target.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"71"},"PeriodicalIF":2.1,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective detection of 148 cases chromosomal mosaicism by karyotyping, chromosomal microarray analysis and QF-PCR in 32,967 prenatal diagnoses.","authors":"Yi Deng, Lan Zeng, Zhiling Wu, Jin Wang, Mengling Ye, Chun Chen, Ping Wei, Danni Wang, Guangming Deng, Shuyao Zhu","doi":"10.1186/s12920-025-02138-z","DOIUrl":"https://doi.org/10.1186/s12920-025-02138-z","url":null,"abstract":"<p><strong>Background: </strong>Detection of mosaicism has always been difficult in prenatal diagnosis, which is to assess the value of karyotyping combined with three different molecular genetic tests for prenatal diagnosis. Retrospective review of chromosomal mosaicism (CM) was conducted in 32,967 pregnant women from January 2015 to December 2022.</p><p><strong>Methods: </strong>A total of 148 fetuses diagnosed with chromosomal mosaicism by karyotyping with copy number variant sequencing (CNV-seq)/ chromosomal microarray analysis (CMA) and quantitative fluorescent polymerase chain reaction (QF-PCR) were selected, and the results from three the methods were compared and further analyzed. The χ2 test for multiple group rates was for the 5 clinical prenatal diagnostic indication groups was used to do multiple comparison tests for statistical analysis. Inconsistent results between methods were identified and further analyzed.</p><p><strong>Results: </strong>A total of 148 CM cases was detected (0.45%, 148/32967), of which karyotyping was detected in combination with CMA in 73 cases (73/85), with CNV-seq in 5 cases (5/11), and with QF-PCR in 35 cases (35/52) and the mosaic conformity rates of the three methods compared with karyotyping were 85.9% (CMA), 67.3% (QF-PCR), and 45.5% (CNV-seq), respectively. There were 49 cases of autosomal mosaicism (49/148, 33.1%) and 99 cases of sex CM (99/148, 66.9%). There were 9 cases of small supernumerary marker chromosome (sSMC)with CMA detection clarified the origin of chromosome fragments. The non-invasive prenatal testing (NIPT) group and the ultrasound abnormality group had the highest detection rates, accounting for 35.1% and 22.3%.</p><p><strong>Conclusions: </strong>In chromosomal mosaicism, there are inconsistent results between different detection methods. Therefore, karyotyping combined with CMA/CNV-seq and FISH methods significantly improves the detection rate of chromosomal mosaicism and also confirms experimental data in the literature, which is of great value for prenatal diagnosis.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"70"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MEIS1 knockdown upregulates WNT signaling pathway genes in esophageal squamous cell carcinoma.","authors":"Nayyerehalsadat Hosseini, Mohammad Mahdi Forghanifard","doi":"10.1186/s12920-025-02134-3","DOIUrl":"https://doi.org/10.1186/s12920-025-02134-3","url":null,"abstract":"<p><strong>Background: </strong>The transcription factor MEIS1 belongs to the 3-amino acid loop extension (TALE) family of homeodomain proteins which plays various functions in normal and tumor cell progression. The canonical WNT/β-catenin pathway governs a plethora of biological processes including cell proliferation, differentiation, and tumor development. In the present study, the effect of MEIS1 gene silencing was assessed on WNT pathway genes in esophageal squamous cell carcinoma (ESCC) cells.</p><p><strong>Materials and methods: </strong>Along with the packaging plasmids, the pLKO.1-MEIS1 plasmid was cotransfected into HEK293T to generate lentiviral particles, followed by transduction of a semi-confluent KYSE-30 cell culture. After total RNA extraction and cDNA synthesis, comparative real-time PCR was applied to assess the efficiency of MEIS1 knockdown and the expression of genes related to the WNT signaling pathway.</p><p><strong>Results: </strong>The results revealed effective downregulation of MEIS1 in KYSE-30 cells. Interestingly, MEIS1 silencing led to a substantial overexpression of WNT pathway key components while the expression of negative regulators of this pathway was substantially decreased.</p><p><strong>Conclusions: </strong>Our data suggest that MEIS1 gene probably induces WNT/β-catenin pathway deactivation in ESCC cells. Consequently, the inverse correlation of MEIS1 expression and WNT signaling pathway activation may introduce a new molecular linkage through ESCC progression and aggressiveness.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"69"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic analysis of four cases of Poirier Bienvenu neurodevelopmental syndrome associated with CSNK2B variant.","authors":"Liu Yang, Daoqi Mei, Yanping Liu, Li Gao","doi":"10.1186/s12920-025-02132-5","DOIUrl":"10.1186/s12920-025-02132-5","url":null,"abstract":"<p><strong>Background: </strong>CSNK2B deficiency underlies the pathogenesis of Poirier-Bienvenu neurodevelopmental syndrome (POBINDS). In this study, we present four cases of pediatric seizures caused by de novo variants in CSNK2B, with the aim to reinforce the clinical and variant data pertaining to early genetic factors associated with epilepsy.</p><p><strong>Methods: </strong>Trio whole exome sequencing were used to detect variants in the proband and her family members, and bioinformatics annotation was performed for the variant. Sanger sequencing and CSNK2B cDNA sequencing were employed to ascertain the carrier status of additional family members and evaluate the potential impact of variants on splicing.</p><p><strong>Results: </strong>All four cases presented with epilepsy as the initial manifestation, accompanied by global developmental delay, particularly in language and motor developmental delay. Cases 1, 3 and 4 exhibited full-scale tonic-clonic seizures, while case 2 displayed myoclonic and typical absence seizures. Furthermore, case 2 demonstrated delayed growth and development compared to age-matched peers. No abnormality was detected in the head magnetic resonance imaging (MRI). Genetic analysis revealed novel heterozygous variants in the CSNK2B gene in all four cases, including c.175 + 1G > A, c.73-2A > G, c.291 + 1G > A and c.481delA. In case 2, reverse transcription analysis of CSNK2B mRNA revealed the retention of the 3' end sequence of Intron 2 and deletion of the 5' end sequence of Exon 3. In treatment, four case received a combination of one to three types of antiseizure medication and rehabilitation training individually. Case 1 continued to experience seizures to varying degrees, while cases 2-4 demonstrated effective seizure control. Overall motor and intellectual development improved in all four cases, however, there was slow recovery in language function.</p><p><strong>Conclusion: </strong>This study elucidates the molecular etiology of epilepsy in four cases with POBINDS and expands the mutational spectrum of pathogenic variants in the CSNK2B, highlighting their impact on splicing. The highly genetic heterogeneous phenotype of POBINDS relies on the detection of pathogenic variants in CSNK2B. Conventional antiseizure medication effectively control seizures, while rehabilitation treatment can significantly improve intelligence and motor function to varying degrees; however, language recovery tends to be relatively slow.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"68"},"PeriodicalIF":2.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic targets related to aging for the treatment of coronary artery disease.","authors":"Kai Huang, Zijun Chen, Ruting Wang, Hangfeng Ying, Jiahao Duan, Yi Zhang, Qianyuan Shi, Chun Yang, Ling Yang","doi":"10.1186/s12920-025-02137-0","DOIUrl":"https://doi.org/10.1186/s12920-025-02137-0","url":null,"abstract":"<p><strong>Background: </strong>Coronary Artery Disease (CAD) is the most common cardiovascular disease worldwide, threatening human health, quality of life and longevity. Aging is a dominant risk factor for CAD. This study aims to investigate the potential mechanisms of aging-related genes and CAD, and to make molecular drug predictions that will contribute to the diagnosis and treatment.</p><p><strong>Methods: </strong>We downloaded the gene expression profile of circulating leukocytes in CAD patients (GSE12288) from Gene Expression Omnibus database, obtained differentially expressed aging genes through \"limma\" package and GenaCards database, and tested their biological functions. Further screening of aging related characteristic genes (ARCGs) using least absolute shrinkage and selection operator and random forest, generating nomogram charts and ROC curves for evaluating diagnostic efficacy. Immune cells were estimated by ssGSEA, and then combine ARCGs with immune cells and clinical indicators based on Pearson correlation analysis. Unsupervised cluster analysis was used to construct molecular clusters based on ARCGs and to assess functional characteristics between clusters. The DSigDB database was employed to explore the potential targeted drugs of ARCGs, and the molecular docking was carried out through Autodock Vina. Finally, single-cell data (GSE159677) of arterial intima was used to further explore the expression of aging signature genes in different cell subpopulations.</p><p><strong>Results: </strong>We identified 8 ARCGs associated with CAD, in which HIF1A and FGFR3 were up while NOX4, TCF7L2, HK3, CDK18, TFAP4, and ITPK1 were down in CAD patients. Based on this, CAD patients can be divided into two molecular clusters, among which cluster A mainly involves functional pathways such as ECM receptor interaction and focal adhesion; cluster B mainly involves functional pathways such as amimo sugar and nucleotide sugar metabolism and pyrimidine metabolism. In addition, the molecular docking results showed that retinoic acid and resveratrol had good binding affinity with targets genes. Further single-cell analysis results showed that NOX4, TCF7L2, ITPK1, and HIF1A were specifically expressed in different types of cells in atherosclerotic tissues.</p><p><strong>Conclusion: </strong>Our study identified several ARCGs that may be involved in the pathogenesis and progression of CAD. Further, retinoic acid and resveratrol were potential candidate molecule drugs for inhibiting these targets.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"66"},"PeriodicalIF":2.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrum of genetic alterations in patients with peroxisome biogenesis defects in the Iranian population: a case series study.","authors":"Sheyda Khalilian, Mohadeseh Fathi, Sanaz Jamshidi, Rasoul Madannejad, Arezou Sayad, Soudeh Ghafouri-Fard, Mohammad Miryounesi","doi":"10.1186/s12920-025-02126-3","DOIUrl":"https://doi.org/10.1186/s12920-025-02126-3","url":null,"abstract":"<p><p>Peroxisomal disorders are a group of hereditary metabolic disorders that happen when peroxisomes are defective. Around 80% of individuals affected by peroxisomal disorders are classified within the spectrum of Zellweger syndromes with autosomal recessive inheritance pattern that results from mutations in one of the 13 PEX genes. Clinical exome sequencing plays a vital role in the diagnosis where the symptoms are atypical. In the current study, we used this technique to find the underlying genetic cause in 14 Iranian patients with peroxisomal disorders. PEX1 variants were detected in five patients. PEX2, PEX5, PEX6 and PEX7 variants were detected in three, one, one, and two cases, respectively. Finally, ACOX1 variants were identified in two cases. All cases except two cases were homozygote for the suspected variants in Zellweger syndrome-related genes. Two cases were compound heterozygote for variants in the PEX1 gene. In total, two novel variants were identified, including c.313 C > T (p.Gln105*) and c.961 A > T (p.Ile321Phe) in the PEX1 and ACOX1 genes, respectively. The present research expands the range of genetic variations observed in Iranian individuals diagnosed with various forms of Zellweger spectrum disorders.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"67"},"PeriodicalIF":2.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Putative function and prognostic molecular marker of mast cells in colorectal cancer.","authors":"Jiani Guo, Jie Chen, Yiting Wang, Xiaoming Bai, Haimei Feng, Siqi Sheng, Hongyu Wang, Ke Xu, Mengxi Huang, Zengjie Lei, Xiaoyuan Chu","doi":"10.1186/s12920-025-02117-4","DOIUrl":"https://doi.org/10.1186/s12920-025-02117-4","url":null,"abstract":"<p><strong>Background: </strong>The increased demand for markers for colorectal cancer (CRC) highlights the importance of investigating immune cells involved in CRC progression. This study aims to dissect the mast cells in CRC, characterize the role of mast cells in CRC development, coordinate molecular communication between mast cells and malignant cells, and construct and validate a prognostic classification model based on mast cell markers.</p><p><strong>Methods: </strong>Single-cell transcriptome data of CRC patients were extracted from GSE146771 for cell classification and annotation. The malignant cells were identified by copykat and the communication between mast cells and malignant cells was analyzed by CellChat. Least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis of mast cell markers were performed in the TCGA-COAD cohort to construct a prognostic classification model. qRT-PCR was performed to detect the mRNA expression of the molecules in the classification model in P815 and MC-9 cells. The co-culture experiment of MC38 and P815 cells were performed in 12-well transwell dish. Wound healing assay and Transwell assay were performed to detect cell migration and invasion.</p><p><strong>Results: </strong>10,186 high-quality cells in GSE146771 were annotated to 9 cell types. Six markers in mast cells (HDC, GATA2, ASAH1, BTBD19, TIMP1, FAM110A) were selected to construct a classification model. The high-risk score defined showed high infiltration of immunosuppressive cells, including endothelial cells, CAFs, Tregs and high angiogenesis and epithelial-mesenchymal transition (EMT) activities. In the model, HDC were abnormally low expressed in P815 cells, while BTBD19, FAM110A, GATA2, ASAH1 and TIMP1 showed excessive expression in P815 cells. Knockdown of GATA2 in the co-culture system of P815 and MC38 cells blocked cell migration and invasion.</p><p><strong>Conclusion: </strong>This study identified the cell types within CRC, elaborated the cellular functions of mast cells in CRC development and their molecular communication to coordinate malignant cells, and highlighted the molecular components and biological features that constitute promising prognostic classification model.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"18 1","pages":"65"},"PeriodicalIF":2.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}