BMC Medical Genomics最新文献

{"title":"Genomic profiling and expanded use of targeted anticancer drugs in solid cancers with exhausted evidence-based treatment options (PRECODE): study protocol of a prospective, non-randomized, cohort study.","authors":"Karin Holmskov Hansen, Maria Bibi Lyng, Annette Raskov Kodahl, Jon Thor Asmussen, Arman Arshad, Henrik Petersen, Lotte Krogh, Sidse Ehmsen, Thomas Kielsgaard Kristensen, Henrik J Ditzel","doi":"10.1186/s12920-024-02033-z","DOIUrl":"10.1186/s12920-024-02033-z","url":null,"abstract":"<p><strong>Background: </strong>Genomic profiling of advanced solid cancer in patients with no further evidence based standard treatment options is a novel approach to identify potential experimental treatment options based on specific genomic alterations. Due to the expected short survival of these patients timely assessment of potential druggable targets is critical to minimize the risk of deterioration during the analysis. The primary objective of this prospective study is to evaluate the turnaround time for genomic profiling and the clinical investigational procedures. The secondary objectives are to investigate how often genomic alterations in tumor tissue gives rise to a matched treatment offer and evaluate the clinical outcome.</p><p><strong>Methods: </strong>The PRECODE study is a prospective, non-randomized, single-center cohort study conducted at Departments of Oncology and Pathology, Odense University Hospital, Denmark. Enrollment between March 1, 2019 and December 31, 2024. Eligibility criteria are age ≥ 18 years, written informed consent, advanced solid tumors, exhausted treatment options, ECOG performance status 0-2, adequate organ function and life expectancy ≥ 3 months. A core needle biopsy is analyzed by next generation sequencing using a pan-cancer comprehensive panel. Results are discussed weekly at institutional/local and national multidisciplinary tumor boards.</p><p><strong>Discussion: </strong>Strategies and methods for genomic profiling of advanced solid cancers differ. Rapid analysis and interpretation of sequencing data are key to avoiding delays in initiation potential experimental treatments, as these late-stage patients may quickly deteriorate. Although a highly optimized setup with fast-track clinical evaluation and genomic profiling has been established a subset will not be offered a targeted treatment due to deterioration. Local and national multidisciplinary teams have been established to optimize individualized treatment decisions. After genomic profiling a subset of patients will take part in clinical trials, which will constrain the reporting of overall survival or progression free survival.</p><p><strong>Trial registration: </strong>Danish Ethics Committee, Projekt-ID: S-2018014, date of approval: 27- FEB- 2019) Danish Data Protection Agency (Journal no: 18/58329, date of approval: 23-NOV-2018).</p><p><strong>Clinicaltrials: </strong>gov Identifier: NCT05385081 (retrospectively registered).</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"274"},"PeriodicalIF":2.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685856","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":"Private detection of relatives in forensic genomics using homomorphic encryption.","authors":"Fillipe D M de Souza, Hubert de Lassus, Ro Cammarota","doi":"10.1186/s12920-024-02037-9","DOIUrl":"10.1186/s12920-024-02037-9","url":null,"abstract":"<p><strong>Background: </strong>Forensic analysis heavily relies on DNA analysis techniques, notably autosomal Single Nucleotide Polymorphisms (SNPs), to expedite the identification of unknown suspects through genomic database searches. However, the uniqueness of an individual's genome sequence designates it as Personal Identifiable Information (PII), subjecting it to stringent privacy regulations that can impede data access and analysis, as well as restrict the parties allowed to handle the data. Homomorphic Encryption (HE) emerges as a promising solution, enabling the execution of complex functions on encrypted data without the need for decryption. HE not only permits the processing of PII as soon as it is collected and encrypted, such as at a crime scene, but also expands the potential for data processing by multiple entities and artificial intelligence services.</p><p><strong>Methods: </strong>This study introduces HE-based privacy-preserving methods for SNP DNA analysis, offering a means to compute kinship scores for a set of genome queries while meticulously preserving data privacy. We present three distinct approaches, including one unsupervised and two supervised methods, all of which demonstrated exceptional performance in the iDASH 2023 Track 1 competition.</p><p><strong>Results: </strong>Our HE-based methods can rapidly predict 400 kinship scores from an encrypted database containing 2000 entries within seconds, capitalizing on advanced technologies like Intel AVX vector extensions, Intel HEXL, and Microsoft SEAL HE libraries. Crucially, all three methods achieve remarkable accuracy levels (ranging from 96% to 100%), as evaluated by the auROC score metric, while maintaining robust 128-bit security. These findings underscore the transformative potential of HE in both safeguarding genomic data privacy and streamlining precise DNA analysis.</p><p><strong>Conclusions: </strong>Results demonstrate that HE-based solutions can be computationally practical to protect genomic privacy during screening of candidate matches for further genealogy analysis in Forensic Genetic Genealogy (FGG).</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"273"},"PeriodicalIF":2.1,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674950","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":"Genome-wide association analysis of cystatin c and creatinine kidney function in Chinese women.","authors":"Yang Cai, Hongyao Lv, Meng Yuan, Jiao Wang, Wenhui Wu, Xiaoyu Fang, Changying Chen, Jialing Mu, Fangyuan Liu, Xincheng Gu, Hankun Xie, Yu Liu, Haifeng Xu, Yao Fan, Chong Shen, Xiangyu Ma","doi":"10.1186/s12920-024-02048-6","DOIUrl":"10.1186/s12920-024-02048-6","url":null,"abstract":"<p><strong>Background: </strong>With increasing incidence and treatment costs, chronic kidney disease (CKD) has become an important public health problem in China, especially in females. However, the genetic determinants are very limited. The estimated glomerular filtration rate (eGFR) based on creatinine is commonly used as a measure of renal function but can be easily affected by other factors. In contrast, eGFR based on both creatinine and cystatin C (eGFRcr-cys) improved the diagnostic accuracy of CKD. To our knowledge, no genome-wide association analysis of eGFRcr-cys has been conducted in the Chinese population.</p><p><strong>Methods: </strong>By conducting a Genome-Wide association study(GWAS), a method used to identify associations between genetic regions (genomes) and traits/diseases, we examined the relationship between genetic factors and eGFRcr-cys in Chinese women, with 1983 participants and 3,838,121 variants included in the final analysis.</p><p><strong>Result: </strong>One significant locus (20p11.21) was identified in the Chinese female population, which has been reported to be associated with eGFR based on cystatin C (eGFRcys) in the European population. More importantly, we found two new suggestive loci (1p31.1 and 11q24.2), which have not yet been reported. A total of three single nucleotide polymorphisms were identified as the most important variants in these regions, including rs2405367 (CST3), rs66588571(KRT8P21), and rs626995 (OR8B2).</p><p><strong>Conclusion: </strong>We identified 3 loci 20p11.21, 1p31.1, and 11q24.2 to be significantly associated with eGFRcr-cys. These findings and subsequent functional analysis describe new biological clues related to renal function in Chinese women and provide new ideas for the diagnosis and treatment development of CKD.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"272"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667313","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":"Elevated expression of APOO as a potential prognostic marker in breast cancer: insights from bioinformatic analysis and experimental validation.","authors":"Yang Bai, Qian Tang, Liang Zheng, Jun He, Wenjian Wang, Liqi Li, Ju Yu","doi":"10.1186/s12920-024-02047-7","DOIUrl":"10.1186/s12920-024-02047-7","url":null,"abstract":"<p><strong>Objective: </strong>Apolipoprotein O (APOO) has been identified through bioinformatic prediction analysis as being highly expressed in various tumors, including breast cancer (BRCA). However, further investigations are required to understand and confirm APOO's biological role in BRCA.</p><p><strong>Methods: </strong>Bioinformatic analyses were employed to identify genes' expression statuses and their relationship with the prognoses of patients. The genes' functions were determined in cell line by gain or loss of function assays. Mechanistic studies were carried out by western blot.</p><p><strong>Results: </strong>Our study reveals a correlation between increased APOO expression and poorer clinical outcomes in BRCA patients. The diagnostic value of APOO was demonstrated by Receiver Operating Characteristic (ROC) curve analysis, showing a notable area under the curve (AUC) of 0.937. Additionally, we observed that APOO knockdown impedes cell proliferation and migration. Gene Set Enrichment Analysis (GSEA) suggests that APOO expression is associated with the regulation of apoptosis and autophagy signaling pathways. Experimentally, modifying APOO expression in vitro influenced apoptosis and autophagy in BRCA cells. In conclusion, our findings indicate a significant link between APOO expression and BRCA progression, mediated through APOO's impact on cellular apoptosis and autophagy.</p><p><strong>Conclusions: </strong>Our data show that APOO controls BRCA process through apoptosis and autophagy signal pathway, which might provide multiple promising choices for the treatment of BRCA.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"271"},"PeriodicalIF":2.1,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667307","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":"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/s12920-024-02049-5","DOIUrl":"10.1186/s12920-024-02049-5","url":null,"abstract":"<p><strong>Background: </strong>LHX3 is a gene encoding a LIM-homeodomain transcription factor important for the fetal development of several organs, such as the pituitary gland, spinal motor neurons and the inner ear. Pathogenic and likely pathogenic variants in the LHX3 gene are infrequent and result in a rare syndrome known as combined pituitary hormone deficiency-3, CPHD3.</p><p><strong>Methods: </strong>We have studied hearing and vestibular functions in a group of eight individuals, aged 8-36 years, all of whom were homozygous for a specific variant in the LHX3 gene at chromosome 9q34. We reexamined the results of consecutive hearing tests from newborn until April 2024.</p><p><strong>Results: </strong>Our data showed that all the tested patients had progressive sensorineural hearing deficiency ranging from moderately severe to complete loss. We have performed vestibular testing in six patients and, for the first time, demonstrated that a mutation in the LHX3 gene not only affects hearing, but is also associated with vestibular impairment.</p><p><strong>Conclusion: </strong>The human pathogenic variant c.455-2A > G in the LHX3 gene on chromosome 9q34, which present as a founder mutation in the population in northern Sweden, is responsible for phenotypes associated with progressive hearing loss and balance impairment. These findings prove that the LHX3 gene is crucial for the function of both the cochlear and vestibular organs.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"270"},"PeriodicalIF":2.1,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643351","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":"Association between miR-30 polymorphism and ischemic stroke in Chinese population.","authors":"Yan-Ping Luo, Xi-Xi Gu, Chao Liu, Ying Huang, Li-Jiang Lu, Shu-Yu Zhang, Yu-Lin Yuan","doi":"10.1186/s12920-024-02041-z","DOIUrl":"10.1186/s12920-024-02041-z","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke (IS) is a commonly seen cerebrovascular disease which seriously endangers the health of middle age and old people. However, its etiology and pathogenesis have not yet fully comprehended. miR-30 gene is a novel gene which may be involved in IS. However, no studies have investigated the relationship between IS and the single-nucleotide polymorphisms (SNPs) of miR-30. Therefore, this study examined the relationship between miR-30 polymorphisms (rs2222722, rs1192037, rs10095483 and rs16827546) and the risk of IS.</p><p><strong>Methods: </strong>Totally 248 IS patients and 230 age-, sex- and race-matched controls were involved in this study. Based on SNPscan technique, four polymorphisms (rs2222722, rs1192037, rs10095483 and rs16827546) were genotyped.</p><p><strong>Results: </strong>There exists a significant association between rs2222722 polymorphism and the risk of IS according to analyses of genotypes, models and alleles (GA vs. GG: adjusted OR = 1.616, 95% CI: 0.943-2.768, P = 0. 081); (AA vs. GG: adjusted OR = 2.447, 95% CI: 1.233-4.858, P = 0.011); dominant model: adjusted (OR = 1.806, 95% CI, 1.082-3.016, P = 0.024); (G vs. A: adjusted OR = 1.492, 95% CI: 1.148-1.939, P = 0.003). Besides, miR-30a expression was significantly higher in patients undergoing IS relative to that in controls (P < 0.05).</p><p><strong>Conclusions: </strong>To conclude, the rs2222722 polymorphism of the miR-30 gene shows a significant relationship to elevate the risk of IS in Chinese population.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"269"},"PeriodicalIF":2.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613781","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":"Comparative meta-analysis of transcriptomic studies in spinal muscular atrophy: comparison between tissues and mouse models.","authors":"Shamini Hemandhar Kumar, Katharina Brandt, Peter Claus, Klaus Jung","doi":"10.1186/s12920-024-02040-0","DOIUrl":"10.1186/s12920-024-02040-0","url":null,"abstract":"<p><strong>Background: </strong>Spinal Muscular Atrophy (SMA), a neuromuscular disorder that leads to weakness in the muscles due to degeneration of motor neurons. Mutations in the survival motor neuron 1 (SMN1) gene leads to the deficiency of SMN protein that causes SMA. The molecular alterations associated with SMA extends across the transcriptome and proteome. Although several studies have examined the transcriptomic profile of SMA, the difference in experimental settings across these studies highlight the need for a comparative meta-analysis to better understand these differences.</p><p><strong>Methods and data: </strong>We conducted a systematic comparative meta-analysis of publicly available gene expression data from six selected studies to elucidate variations in the transcriptomic landscape across different experimental conditions, including tissue types and mouse models. We used both microarray and RNA-seq datasets, retrieved from Gene Expression Omnibus (GEO) and ArrayExpress (AE). Methods included normalization, differential expression analysis, gene-set enrichment analysis (GSEA), network reconstruction and co-expression analysis.</p><p><strong>Results: </strong>Differential expression analysis revealed varying numbers of differentially expressed genes ranging between zero and 1,655 across the selected studies. Notably, the Metallothionein gene Mt2 was common in several of the eight comparisons. This highlights its role in oxidative stress and detoxification. Additionally, genes such as Hspb1, St14 and Sult1a1 were among the top ten differentially expressed genes in more than one comparison. The Snrpa1 gene, involved in pre-mRNA splicing, was upregulated in the spinal cord and has a strong correlation with other differentially expressed genes from other comparisons in our network reconstruction analysis. Gene-set enrichment analysis identified significant GO terms such as contractile fibers and myosin complexes in more than one comparison which highlights its significant role in SMA.</p><p><strong>Conclusions: </strong>Our comparative meta-analysis identified only few genes and pathways that were consistently dysregulated in SMA across different tissues and experimental settings. Conversely, many genes and pathways appeared to play a tissue-specific role in SMA. In comparison with the original studies, reproducibility was rather weak.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"266"},"PeriodicalIF":2.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613791","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 systematic review and meta-analysis of carbapenem-resistant Enterobacteriaceae in West Africa.","authors":"Namwin Siourimè Somda, Rabbi Nyarkoh, Fleischer C N Kotey, Patience B Tetteh-Quarcoo, Eric S Donkor","doi":"10.1186/s12920-024-02043-x","DOIUrl":"10.1186/s12920-024-02043-x","url":null,"abstract":"<p><strong>Background: </strong>In Africa, the problem of carbapenem-resistant Enterobacteriaceae (CRE) is aggravated by many factors. This systematic review attempted to describe the current status of the molecular epidemiology of carbapenem resistance in West Africa (WA).</p><p><strong>Methods: </strong>Articles published from 16 West African countries on the molecular epidemiology of carbapenem resistance were reviewed. An extensive literature search was carried out in PubMed, Scopus, Web of Science, and African Journals Online (AJOL) using specific keywords. The meta-analysis and forest plots of major pathogens and carbapenem resistance genes were done using the Open Meta-Analyst, Task Order # 2 software. The data were analysed in binary random model effects by the DerSimonian-Laird method at a 95% confidence interval.</p><p><strong>Results: </strong>Of the 431 articles found in our initial search, 60 (13.92%) were considered suitable for inclusion. Only seven of the 16 West African countries formed part of the analysis, Nigeria (23/60), Ghana (19/60), Burkina Faso (7/60), Senegal (6/60), Benin (2/60), Mali (2/60), and Togo (1/60). Also, 80% (48/60) of the studies used clinical samples, 16.67% (10/60) used environmental samples, and 3.33% (2/60) used animal samples. The average prevalence was highest in Acinetobacter baumannii (18.6%; 95% CI = 14.0-24.6, I² = 97.9%, p < 0.001), followed by Pseudomonas aeruginosa (6.5%; 95% CI = 3.1-13.4, I² = 96.52%, p < 0.001), Klebsiella pneumoniae (5.8%; 95% CI = 4.2-7.9, I² = 98.06%, p < 0.001) and Escherichia coli (4.1%; 95% CI = 2.2-7.7, I² = 96.68%, p < 0.001). The average prevalence of the blaNDM gene was 10.6% (95% CI = 7.9-14.3, I² = 98.2%, p < 0.001), followed by 3.9% (95% CI: 1.8-8.3, I² = 96.73%, p < 0.001) for blaVIM and 3.1% (95% CI: 1.7-5.8, I² = 91.69%, p < 0.001) for blaOXA-48.</p><p><strong>Conclusion: </strong>In West Africa, K. pneumoniae, E. coli, A. baumannii, and P. aeruginosa are the main CRE with blaNDM, blaVIM, and blaOXA-48 being the predominant carbapenem resistance genes. In view of these results, ongoing CRE surveillance combined with antimicrobial stewardship improved, laboratory detection methods, and adherence to infection control practices will be needed to control the spread of CRE.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"267"},"PeriodicalIF":2.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613658","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: Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing.","authors":"Perihan Hamdy Kassem, Iman Fawzy Montasser, Mohamed Ramy Mahmoud, Rasha Ahmed Ghorab, Dina A AbdelHakam, Marium El Sayed Ahmad Fathi, Marwa A Abdel Wahed, Khaled Mohey, Mariam Ibrahim, Mohamed El Hadidi, Yasmine M Masssoud, Manar Salah, Arwa Abugable, Mohamad Bahaa, Sherif El Khamisy, Mahmoud El Meteini","doi":"10.1186/s12920-024-02045-9","DOIUrl":"https://doi.org/10.1186/s12920-024-02045-9","url":null,"abstract":"","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"268"},"PeriodicalIF":2.1,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11559073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613797","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":"Overexpression of CDCA8 predicts poor prognosis and drug insensitivity in lung adenocarcinoma.","authors":"Huiquan Gu, Xinzheng Gao, Wenlong Han, Fangyu Wang, Hanqiang Zhang, Longyu Yao, Weimin Chen, Qiang Liu","doi":"10.1186/s12920-024-02019-x","DOIUrl":"10.1186/s12920-024-02019-x","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) accounts for the highest proportion of lung cancers; however, specific biomarkers are lacking for diagnosis, treatment, and prognostic assessment. Cell division cycle-associated 8 (CDCA8) is a cell cycle regulator with elevated expression in various cancers. However, the association between CDCA8 expression and LUAD prognosis remains unclear.</p><p><strong>Methods: </strong>The association between CDCA8 and LUAD prognosis was evaluated based on the The Cancer Genome Atlas (TCGA) dataset, and CDCA8 related functions were determined using gene enrichment and gene ontology analyses. We also analyzed the association between CDCA8 expression and immune cell infiltration. Immunohistochemistry was used to determine the differential expression of CDCA8 in tumors and controls. Finally, we evaluated the differences in the sensitivity of different levels of CDCA8 to different anticancer drugs in LUAD.</p><p><strong>Results: </strong>CDCA8 expression was significantly higher in primary LUAD tumors than in normal tissues (P < 0.001). Moreover, Kaplan-Meier survival analysis demonstrated that high CDCA8 expression predicted poor survival in patients with LUAD (P = 0.006). The receiver operating characteristic (ROC) curves indicated that CDCA8 was an effective guide for the diagnosis of LUAD. Functional annotation indicated that CDCA8 might be involved in functions such as p53 stabilization, nucleotide metabolism, RNA-mediated gene silencing, and the G2/M phase checkpoint. Immune infiltration results suggested that CDCA8 was positively correlated with Th2 cells and Tgd and negatively correlated with Eosinophils and Mast cells (P < 0.01). In addition, elevated expression of CDCA8 may increase the sensitivity of patients to certain anticancer drugs.</p><p><strong>Conclusions: </strong>CDCA8 upregulation is significantly associated with poor survival and immune infiltration in patients with LUAD. Our study suggests that CDCA8 can be used as a biomarker for LUAD prognosis and a reference for personalized medication.</p>","PeriodicalId":8915,"journal":{"name":"BMC Medical Genomics","volume":"17 1","pages":"265"},"PeriodicalIF":2.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613801","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}