BMC Medical Genomics最新文献

{"title":"CLOCK gene 3'UTR and exon 9 polymorphisms show a strong association with essential hypertension in a North Indian population.","authors":"Shreya Sopori, Kavinay Kavinay, Sonali Bhan, Shreya Saxena, Medha Medha, Rakesh Kumar, Arti Dhar, Audesh Bhat","doi":"10.1186/s12920-024-02056-6","DOIUrl":"10.1186/s12920-024-02056-6","url":null,"abstract":"<p><strong>Background: </strong>Hypertension (HTN) is a medical condition characterized by persistent systolic and diastolic blood pressures of ≥ 140 mmHg and ≥ 90 mmHg, respectively. With more than 1200 million adult patients aged 30-79 years worldwide according to the latest WHO data, HTN is a major health risk factor; more importantly, 46% of patients are unaware of this condition. Essential hypertension (EH), also known as primary hypertension, is the predominant subtype and has a complex etiology that involves both genetic and non-genetic factors. Majority of living organisms are influenced by the light and dark cycle of a day and respond to these changes through an intricate clock referred to as the \"biological clock\" or \"circadian rhythm\". The connection between circadian rhythm and blood pressure is well established, with many studies supporting the role of circadian rhythm gene mutation(s)/polymorphism(s) in EH. To date, no such data are available from any Indian population.</p><p><strong>Methods: </strong>This case‒control study was conducted on 405 EH patients and 505 healthy controls belonging to the Jammu region of North India after an informed consent was obtained from the participants. A total of three single nucleotide variants, two in the CLOCK gene (rs1801260 and rs34789226) and one in the BMAL1/ARNTL gene (rs6486121), were selected for genotyping. Genotyping was performed via the RFLP technique, and the applicable statistical analyses were performed via the SPSS and SNPStats programs.</p><p><strong>Results: </strong>Logistic regression analysis revealed a statistically significant association of both CLOCK gene variants rs1801260 (T > C 3'UTR) and rs34789226 (C > T Exon 9) and a nonsignificant association of the BMAL1/ARNTL intronic variant rs6486121 (C > T) with EH. The 3'UTR variant showed a statistically significant association under the codominant (p < 0.0001), dominant (p < 0.0001), and recessive (p = 0.0004) models. In contrast, the exon 9 variant showed a statistically significant negative association under the codominant (p = 0.003) and dominant (p = 0.015) models only. The rs6486121/rs1801260 and rs1801260/rs34789226/rs6486121 haplotypes showed significant differences in their distribution between cases and controls (p < 0.0001). Certain genotypes and haplotypes were found more common in hypertensive males than females.</p><p><strong>Conclusion: </strong>This is a first report linking circadian rhythm gene polymorphisms with EH in any Indian population. The statistically significant association of the CLOCK gene 3'UTR and exon 9 polymorphisms with EH, highlight the potential role of this gene and probably other genes of the circadian pathway in the etiology of EH in the study population. Additionally, our study also revealed that certain genotypes are making males more susceptible to EH.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"289"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852136","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":"THBS1 is a new autosomal recessive non-syndromic hearing impairment gene.","authors":"Thashi Bharadwaj, Anushree Acharya, Fati Ullah Khan, Saadullah Khan, Irfan Ullah, Isabelle Schrauwen, Wasim Ahmad, Suzanne M Leal","doi":"10.1186/s12920-024-02060-w","DOIUrl":"10.1186/s12920-024-02060-w","url":null,"abstract":"<p><strong>Background: </strong>Prelingual hearing impairment (HI) is genetically highly heterogenous. Early diagnosis and intervention are essential for psychosocial development. In this study we investigated a consanguineous family from Pakistan with autosomal recessive (AR) non-syndromic sensorineural HI (NSHI).</p><p><strong>Methods: </strong>A DNA sample from an HI member of a consanguineous Pakistani family segregating ARNSHL underwent exome sequencing. Using Sanger sequencing select variants were validated and tested for segregation using DNA samples from additional family members. We further investigated RNA expression data for the candidate gene in mouse and human inner ear and human inner ear organoids using data obtained from the gene Expression Analysis Resource.</p><p><strong>Results: </strong>We identified thrombospondin 1 (THBS1) as a new NSHI gene. A homozygous frameshift variant [c.1470del: p.(Ile491Serfs*45)] was observed in the three hearing-impaired and in the heterozygous state in three unaffected family members. Unlike for most ARNSHI, hearing-impaired individuals had audiograms with a sloping pattern, showing more pronounced HI in the mid and high frequencies (ranging from moderate to profound) compared to the low frequencies. RNA expression data indicates THBS1 is expressed during human inner ear development. Additionally, THBS1 is expressed in the cochlear epithelium and supporting cells of the mouse inner ear during embryonic and postnatal stages. Previously, THBS1 was demonstrated to affect hearing in knockout mice by influencing the formation and function of afferent synapses in the inner ear.</p><p><strong>Conclusions: </strong>Our findings highlight THBS1 as a potential novel candidate gene for human HI characterized by a sloping high-frequency audio profile. This discovery enhances our understanding of the genetic etiology of HI and will aid in advancing molecular diagnosis.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"291"},"PeriodicalIF":2.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852154","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":"Correction: Hearing impairment and vestibular function in patients with a pathogenic splice variant in the LHX3 gene.","authors":"Åsa Kjellgren, Elenor Lundgren, Irina Golovleva, Berit Kriström, Mimmi Werner","doi":"10.1186/s12920-024-02062-8","DOIUrl":"10.1186/s12920-024-02062-8","url":null,"abstract":"","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"285"},"PeriodicalIF":2.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799176","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":"Correlation between rs7041 and rs4588 polymorphisms in vitamin D binding protein gene and COVID-19-related severity and mortality.","authors":"Eman Riad Hamed, Shaymaa Abdelraheem Abdelhady, Shimaa A Al-Touny, Rania M Kishk, Marwa Hussein Mohamed, Fatma Rageh, Amira Ahmed Abdelrahman Othman, Wagdy Abdelfatah, Hasnaa Azab","doi":"10.1186/s12920-024-02018-y","DOIUrl":"10.1186/s12920-024-02018-y","url":null,"abstract":"<p><strong>Background: </strong>The vitamin D binding protein (DBP) plays a critical role in both innate and adaptive immune systems, participating in several clinical conditions, including coronavirus disease 2019 infection severity, and mortality rate. The study aimed to investigate the correlation between rs7041 and rs4588 polymorphisms in the DBP gene and Coronavirus Disease-2019 (COVID-19) severity and mortality, in patients of Suez Canal University Hospitals in Ismailia, Egypt.</p><p><strong>Methods: </strong>A case-control study enrolled 220 individuals; 140 COVID-19 patients and 80 healthy controls. Serum 25(OH) vitamin D levels were determined by the enzyme-linked immunosorbent assay (ELISA), and rs7041 and rs4588 polymorphisms of the DBP gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).</p><p><strong>Results: </strong>The study found that both groups had vitamin D deficiency, which was considerably lower in the COVID-19 patients group compared to controls. Among COVID-19 patients, there was a significant difference in vitamin D levels according to the disease severity indicating that vitamin D levels can be used as predictors of COVID-19 severity. Negative significant correlations between genetic variants rs4588 CA genotype and genetic variants rs7041 TT genotype and COVID-19 prevalence (p = 0.006 and 0.009 respectively) were proved. No significant correlations between all the genetic variants of both rs4588 and rs7041 and COVID-19 severity (p > 0.05). Positive significant correlations between both genetic variants rs4588 CA genotype and genetic variants rs7041 TG genotype and COVID-19 mortality (p = 0.029 and 0.031 respectively).</p><p><strong>Conclusion: </strong>vitamin D deficiency increased the severity of COVID-19. The DBP polymorphism correlated with vitamin COVID-19 prevalence and mortality.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"284"},"PeriodicalIF":2.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765668","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":"Sex differences in MAGEL2 gene promoter methylation in high functioning autism - trends from a pilot study using nanopore Cas9 targeted long read sequencing.","authors":"Jelte Wieting, Kirsten Jahn, Stefan Bleich, Maximilian Deest, Helge Frieling","doi":"10.1186/s12920-024-02053-9","DOIUrl":"10.1186/s12920-024-02053-9","url":null,"abstract":"<p><strong>Background: </strong>MAGEL2 is an autism susceptibility gene whose deficiency has been associated with autism-related behaviors in animal models and in syndromic human autism spectrum disorders (ASDs) such as Schaaf-Yang syndrome, but has not been studied in the broader autism spectrum. Given the capabilities of long-read sequencing technologies, this pilot study used a targeted nanopore sequencing approach to simultaneously examine MAGEL2 DNA sequence and methylation in adults with high-functioning autism (HFA) compared to neurotypical controls (NC).</p><p><strong>Methods: </strong>Using DNA extracted from peripheral blood, Cas9-targeted nanopore DNA sequencing was used to analyze MAGEL2, including its entire regulatory construct (chr15:23639316-23651466), for sequence variation and 5-methyl-cytosine (5mC) modification in a cohort of adults with HFA compared to sex- and age-matched NC. Given the known sex differences in ASD and MAGEL2 KO animal models, results were further analyzed by sex.</p><p><strong>Results: </strong>20 adults with HFA (10 males, 10 females) and 20 NC were included. While there were no overall differences in MAGEL2 DNA sequence and 5mC modification between HFA and NC, we found a significant difference in MAGEL2 gene promoter methylation between males and females with HFA and NC of both sexes, with HFA males tending to show hypomethylation in a 300 bp long differentially methylated region (chr15:23647640-23647939) around the MAGEL2 transcription start site.</p><p><strong>Conclusions: </strong>In this pilot study utilizing nanopore Cas9 targeted DNA sequencing, significant sex-specific differences in MAGEL2 gene promoter methylation were identified in male adults with HFA in comparison to control groups, suggesting the potential for sex-specific epigenetic differences. However, further replication in larger cohorts is required to validate these findings.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"279"},"PeriodicalIF":2.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749823","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":"A novel frameshift variant in the TMPRSS3 gene causes nonsyndromic hearing loss in a consanguineous family.","authors":"Nahid Rezaie, Saeedeh Sadat Ghazanfari, Seyede Mahsa Mousavikia, Nader Mansour Samaei, Morteza Oladnabi, Abdolazim Sarli, Teymoor Khosravi","doi":"10.1186/s12920-024-02055-7","DOIUrl":"10.1186/s12920-024-02055-7","url":null,"abstract":"<p><strong>Background: </strong>Hearing Loss (HL) is the most common sensorineural condition in humans. Mutations in the TMPRSS3 gene (DNFB8/10 locus) have been linked to autosomal recessive non-syndromic hearing loss (ARNSHL).</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was utilized to identify disease-causing variants in a proband from Iran with ARNSHL who presented clinically with sensorineural, bilateral, and prelingual HL. The pathogenicity and novelty of the identified variant were assessed using various databases. A co-segregation study was also performed to confirm the presence of the variant in the proband's parents. Additionally, the secondary and tertiary structures of the mutant TMPRSS3 protein were predicted using bioinformatics tools. Furthermore, a global mutational spectrum of TMPRSS3 was created and statistically analyzed. The Iranome database was also used to identify other putative mutations in the TMPRSS3 gene in the Iranian population.</p><p><strong>Results: </strong>We identified a novel homozygous single nucleotide deletion in TMPRSS3 (c.297delA, p.Asp100ThrfsTer52) in the proband. This is the first report of this mutation in a patient with ARNSHL. Sanger sequencing confirmed that this variant co-segregated from the proband's parents. Bioinformatic tools classified this novel variant as likely pathogenic. Additionally, 49.55% of families with TMPRSS3-related HL patients were shown to have consanguinity, consistent with our study. The Iranome database also revealed the c.268G > A variant as a putative novel mutation in TMPRSS3.</p><p><strong>Conclusion: </strong>This research expanded the pool of evidence regarding the association between mutations in the TMPRSS3 gene and ARNSHL. The finding confirmed that a single nucleotide deletion caused HL in the proband, suggesting that genetic testing, such as WES, is a robust technique for diagnosing patients with this condition.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"283"},"PeriodicalIF":2.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754536","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":"Hereditary thrombotic thrombocytopenic purpura mimicking immune thrombocytopenia was revealed by miscarriage-novel compound heterozygous mutations in hTTP.","authors":"Ruiqing Zhou, Jiahuan Wang, Ahui Wang, Shunqing Wang, Yumiao Li, Shilin Xu, Wenjian Mo","doi":"10.1186/s12920-024-02051-x","DOIUrl":"10.1186/s12920-024-02051-x","url":null,"abstract":"<p><p>We report a case of early-onset hereditary thrombotic thrombocytopenic purpura in a 16-year-old girl who suffered from thrombocytopenia and was misdiagnosed with immune thrombocytopenia for years until two failed gestations finally revealed the underlying cause. The novel compound heterozygous mutation c.2865G > A:p.Trp955X and c.721delG: p.Gly241fs in the ADAMTS13 gene were identified and are predicted to be associated with this disease. The patient responded to plasma therapy, including plasma infusion and plasma exchange, but renal dysfunction may be longstanding.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"281"},"PeriodicalIF":2.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754541","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":"Proteomic analysis illustrates the potential involvement of dysregulated ribosome-related pathways and disrupted metabolism during retinoic acid-induced cleft palate development.","authors":"Wancong Zhang, Liyun Chen, Aiwei Ma, Wenshi Jiang, Mengjing Xu, Xujue Bai, Jianda Zhou, Shijie Tang","doi":"10.1186/s12920-024-02054-8","DOIUrl":"10.1186/s12920-024-02054-8","url":null,"abstract":"<p><p>Recent studies have unveiled disrupted metabolism in the progression of cleft palate (CP), a congenital anomaly characterized by defective fusion of facial structures. Nonetheless, the precise composition of this disrupted metabolism remains elusive, prompting us to identify these components and elucidate primary metabolic irregularities contributing to CP pathogenesis. We established a murine CP model by retinoic acid (RA) treatment and analyzed control and RA-treated embryonic palatal tissues by LC-MS-based proteomic approach. We identified 220 significantly upregulated and 224 significantly downregulated proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that these differentially expressed proteins (DEPs) were involved in translation, ribosome assembly, mitochondrial function, mRNA binding, as well as key metabolic pathways like oxidative phosphorylation (OXPHOS), glycolysis/gluconeogenesis, and amino acid biosynthesis. These findings suggest that dysregulated ribosome-related pathways and disrupted metabolism play a critical role in CP development. Protein-protein interaction analysis using the STRING database revealed a tightly connected network of DEPs. Furthermore, we identified the top 10 hub proteins in CP using the Cytohubba plugin in Cytoscape. These hub proteins, including RPL8, RPS11, ALB, PA2G4, RPL23, RPS6, CCT7, EGFR, HSPD1, and RPS28, are potentially key regulators of CP pathogenesis. In conclusion, our comprehensive proteomic analysis provides insights into the molecular alterations associated with RA-induced CP in Kun Ming mice. These findings suggest potential therapeutic targets and pathways to understand and prevent congenital craniofacial anomalies.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"280"},"PeriodicalIF":2.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754544","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":"ASXL1 truncating variants in BOS and myeloid leukemia drive shared disruption of Wnt-signaling pathways but have differential isoform usage of RUNX3.","authors":"Isabella Lin, Zain Awamleh, Mili Sinvhal, Andrew Wan, Leroy Bondhus, Angela Wei, Bianca E Russell, Rosanna Weksberg, Valerie A Arboleda","doi":"10.1186/s12920-024-02039-7","DOIUrl":"10.1186/s12920-024-02039-7","url":null,"abstract":"<p><strong>Background: </strong>Rare variants in epigenes (a.k.a. chromatin modifiers), a class of genes that control epigenetic regulation, are commonly identified in both pediatric neurodevelopmental syndromes and as somatic variants in cancer. However, little is known about the extent of the shared disruption of signaling pathways by the same epigene across different diseases. To address this, we study an epigene, Additional Sex Combs-like 1 (ASXL1), where truncating heterozygous variants cause Bohring-Opitz syndrome (BOS, OMIM #605039), a germline neurodevelopmental disorder, while somatic variants are driver events in acute myeloid leukemia (AML). No BOS patients have been reported to have AML.</p><p><strong>Methods: </strong>This study explores common pathways dysregulated by ASXL1 variants in patients with BOS and AML. We analyzed whole blood transcriptomic and DNA methylation data from patients with BOS and AML with ASXL1-variant (AML-ASXL1) and examined differential exon usage and cell proportions.</p><p><strong>Results: </strong>Our analyses identified common molecular signatures between BOS and AML-ASXL1 and highlighted key biomarkers, including VANGL2, GRIK5 and GREM2, that are dysregulated across samples with ASXL1 variants, regardless of disease type. Notably, our data revealed significant de-repression of posterior homeobox A (HOXA) genes and upregulation of Wnt-signaling and hematopoietic regulator HOXB4. While we discovered many shared epigenetic and transcriptomic features, we also identified differential splice isoforms in RUNX3 where the long isoform, p46, is preferentially expressed in BOS, while the shorter p44 isoform is expressed in AML-ASXL1.</p><p><strong>Conclusion: </strong>Our findings highlight the strong effects of ASXL1 variants that supersede cell-type and even disease states. This is the first direct comparison of transcriptomic and methylation profiles driven by pathogenic variants in a chromatin modifier gene in distinct diseases. Similar to RASopathies, in which pathogenic variants in many genes lead to overlapping phenotypes that can be treated by inhibiting a common pathway, our data identifies common pathways for ASXL1 variants that can be targeted for both disease states. Comparative approaches of high-penetrance genetic variants across cell types and disease states can identify targetable pathways to treat multiple diseases. Finally, our work highlights the connections of epigenes, such as ASXL1, to an underlying stem-cell state in both early development and in malignancy.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"282"},"PeriodicalIF":2.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754540","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":"Construction of an immunogenic cell death-related LncRNA signature to predict the prognosis of patients with lung adenocarcinoma.","authors":"Shuaishuai Wang, Yi Zhang","doi":"10.1186/s12920-024-02042-y","DOIUrl":"10.1186/s12920-024-02042-y","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is one of the most common malignant diseases worldwide. This study aimed to construct an immunogenic cell death (ICD)-related long non-coding RNA (lncRNA) signature to effectively predict the prognosis of LUAD.</p><p><strong>Methods: </strong>The RNA-sequencing and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA). Least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox proportional hazard regression analysis were utilized to construct lncRNA signature. Then, the reliability of the signature was evaluated in the training, validation and whole cohorts. The differences in the immune landscape and drug sensitivity between the low- and high-risk groups were analyzed. Finally, the expression level of the selected ICD-related lncRNAs in LUAD cell lines via reverse transcription quantitative PCR (RT-qPCR). CCK-8 and transwell assays were performed to study biological function of AC245014.3.</p><p><strong>Results: </strong>A signature consisting of 5 ICD-related lncRNAs was constructed. Kaplan Meier (K-M) survival analysis showed shorter overall survival (OS) in high-risk group. The receiver operating characteristic (ROC) curves and Multivariate Cox regression analysis showed the signature was good predictive and independent prognostic factor in LUAD. Moreover, the high-risk group had a lower level of antitumor immunity and was less sensitive to some chemotherapeutics and targeted drugs. Finally, the expression level of selected ICD-related lncRNAs was validated in LUAD cell lines by RT-qPCR. Knockdown of AC245014.3 significantly suppressed LUAD proliferation, migration and invasion.</p><p><strong>Conclusions: </strong>In this study, an ICD-related lncRNA signature was constructed, which could accurately predict the prognosis of LUAD patients and guide clinical treatment.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"277"},"PeriodicalIF":2.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738290","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}