BMC Medical Genomics最新文献

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: To conclude, the rs2222722 polymorphism of the miR-30 gene shows a significant relationship to elevate the risk of IS in Chinese population.

Background: 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.

Methods and data: 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.

Results: 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.

Conclusions: 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.

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Numerous studies have demonstrated the involvement of messenger RNAs (mRNAs) and non-coding RNAs, including long non-coding RNAs (lncRNA), circular RNAs (circRNAs) and microRNA (miRNAs), in gouty arthritis onset; however, the regulatory mechanism has not yet been elucidated. Here, we applied whole-transcriptome sequencing to identify the differentially expressed circRNAs, lncRNAs, miRNAs and mRNAs between the gout patients and normal people, and constructed co-regulated networks of circRNAs and lncRNAs according to the competitive endogenous RNA (ceRNA) theory for gouty arthritis onset to improve our understanding of the pathogenesis of this disease. The most significant finding of this study is the co-regulated ceRNA network of circRNAs and lncRNAs in gouty arthritis. The circRNA novel_circ_0030384 and the lncRNAs AAMP, TRIM16, PKN1, XLOC_184579 and XLOC_189826 were upstream genes in the co-regulated network. These upstream genes upregulated miR550a-5p and miR550a-3-5p, which downregulated PSME1 and FERMT3 expression. These mRNAs participated in proteasome dynamics, antigen processing and presentation, and platelet activation, which are associated with inflammation in gouty arthritis. In addition, the circRNA and lncRNAs upregulated miR550a-5p, which downregulated GRK2 and OS9 expression. Also, it proved that the down-regulated of PSME1, FERMT3, GRK2 and OS9 can aggravate gouty arthritis in vitro. In summary, these genes mediate inflammation in gouty arthritis through chemokine signaling to regulate neutrophil function.

Background: The copy number status (CNS) of the survival motor neuron (SMN) gene may influence the risk and prognosis of amyotrophic lateral sclerosis (ALS) and lower motor neuron diseases (LMND) other than spinal muscular atrophy (SMA). However, previous studies of this association, mainly from Europe, have yielded controversial results, suggesting possible regional differences. Here, we investigated the effect of the SMN gene in Japanese patients with ALS and LMND.

Methods: We examined the SMN copy numbers and clinical histories of 487 Japanese patients with sporadic ALS (281 men; mean age at onset 61.5 years), 50 with adult LMND (50 men; mean age at onset 58.4 years) and 399 Japanese controls (171 men; mean age 62.2 years). Patients with pathogenic mutations in ALS-causing genes were excluded. SMN1 and SMN2 copy numbers were determined using the droplet digital polymerase chain reaction.

Results: The frequency of a copy number of one for the SMN2 gene was higher in patients with ALS (38.0%) than in healthy controls (30.8%) (odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.04-1.82, p < 0.05). The SMN2 copy number affected the survival time of patients with ALS (median time: 0 copies, 34 months; 1 copy, 39 months; 2 copies, 44 months; 3 copies, 54 months; log-rank test, p < 0.05). Cox regression analysis revealed that the SMN2 copy number was associated with increased mortality (hazard ratio = 0.84, 95% CI = 0.72-0.98, p < 0.05). Also, null SMN2 cases were significantly more frequent in the LMND group (12.0%) than in the control group (4.8%) (OR = 2.73, 95% CI = 1.06-6.98, p < 0.05).

Conclusions: Our findings suggest that SMN2 copy number reduction may adversely affect the onset and prognosis of MND, including ALS and LMND, in Japanese.

Background: Coffin-Siris syndrome is a clinically elusive and rare genetic disease characterized by a wide range of clinical manifestations. This study deeply analyzed and identified the clinical phenotype and genetic variant location in a pediatric patient with Coffin-Siris syndrome, aiming to enhance the understanding of this syndrome and assist in its screening and diagnosis.

Methods: A combination of advanced diagnostic tools, including high-throughput whole-exome sequencing (WES) and first-generation sequencing technologies, was employed to ascertain the etiology of the disease in the child.

Results: The clinical phenotype was characterized by stunted growth, reduced stature, spina bifida, enuresis, and a ventricular septal defect. WES revealed a de novo variant in the SOX11 gene locus (c.700G > T), identified as pathogenic. It is noteworthy that this variant has not been previously reported.

Conclusions: The combination of clinical presentation and genetic testing results supports that the patient suffers from Coffin-Siris syndrome due to a genetic variant in the SOX11 gene. This de novo variant expands our understanding of human gene variation, which is conducive to genetic counseling and screening for early diagnosis of Coffin-Siris syndrome.