Genetics research最新文献

Background: Gastric cancer poses a substantial public health burden, with rising mortality rates in metastatic stages. Elucidating the molecular mechanisms underlying lymph node metastasis is critical for developing novel therapeutic interventions. Methods: Using data from the Cancer Genome Atlas (TCGA), we stratified gastric cancer patients by lymph node metastasis stage (N0-N3) to identify key molecular determinants of metastatic progression. Integrated bioinformatic analyses included differential gene expression profiling, protein-protein interaction networks, survival analysis, and immune microenvironment characterization, with a focused investigation of THPO. Results: We identified metastasis-associated genes, notably THPO, which exhibited stage-dependent upregulation in advanced lymph node metastasis (N3). Elevated THPO expression correlated significantly with adverse prognostic outcomes, including reduced overall survival, disease-free survival, and progression-free survival (all p < 0.05). Mechanistically, THPO promoted epithelial-mesenchymal transition and showed a positive correlation with M2 macrophage infiltration, implicating it in tumor progression. Furthermore, a THPO-centric prognostic signature demonstrated high accuracy in predicting 1-, 3-, and 5-year survival rates (AUC > 0.80), supporting its clinical utility. Furthermore, THPO knockdown in MKN-45 cells suppressed migration and blunted the EMT pathway, confirming its prometastatic role in gastric cancer. Conclusion: Our findings establish THPO as a promising biomarker and therapeutic target in gastric cancer. Molecular insights into lymph node metastasis may facilitate the development of precision prognostic tools and tailored therapeutic strategies, highlighting the imperative for further mechanistic and translational studies.

[This corrects the article DOI: 10.1155/genr/2340176.].

Breast cancer ranks among the top causes of cancer-related deaths in women around the globe, with genetic mutations in the BRCA1 gene being a frequent cause of breast or ovarian cancer. This study investigates hotspot mutations in exon 11 of the BRCA1 gene among Pakistani women diagnosed with breast cancer. Thirty clinically diagnosed breast cancer patients, all women, were enrolled in the current study, and high-quality DNA was extracted from peripheral blood samples. Two of the twenty-five successfully sequenced samples had a homozygous missense variant (c.2312T > C: p.Leu771Ser) detected by Sanger sequencing after PCR amplification. Upon investigation in the ClinVar database, the identified variant showed conflicting interpretations of pathogenicity. Demographic data highlighted an early disease onset, showing that 56% of patients were under 50 years of age. The need for genetic screening was further supported by the fact that 24% of the patients had a positive family history of cancer. Our study emphasizes the necessity of screening BRCA1 gene mutations to better understand the pathogenic potential of the identified variants in the Pakistani population.

Background: Lung adenocarcinoma (LUAD) remains one of the leading causes of cancer-related mortality worldwide. However, the expression and role of TIPE3 and RAC1 in LUAD are not well characterized. Objective: This study aimed to investigate the expression and clinicopathological significance of TNFAIP8L3 (TIPE3) and RAC1 in LUAD, as well as the relationship between these two proteins. Methods: Immunohistochemistry (IHC) was utilized to detect the expression of TIPE3 and RAC1 in tumor and adjacent normal tissues from 183 LUAD patients. A comprehensive analysis of clinicopathological data and subsequent follow-up outcomes was conducted in relation to TIPE3 and RAC1 expression levels. The correlation between these two proteins was also evaluated. Results: Both TIPE3 and RAC1 expression were upregulated in tumor tissues of LUAD. TIPE3 expression was significantly associated with advanced T stage (p=0.001), N stage (p=0.005), and TNM stage (p=0.001). Similarly, increased RAC1 expression was also associated with advanced T stage (p=0.003), N stage (p=0.003), and TNM stage (p=0.001). Kaplan-Meier survival analysis and Cox regression modeling demonstrated that increased TIPE3 and RAC1 expression were independent prognostic factors for poor outcomes in LUAD. Furthermore, Spearman correlation analysis revealed a positive association between TIPE3 and RAC1 expression (r = 0.305, p < 0.001). Combined expression of TIPE3 and RAC1 improved risk stratification and prognostic prediction in LUAD. Conclusion: TIPE3 and RAC1 serve as potential biomarkers of tumor progression and poor prognosis in LUAD, offering promising targets for future therapeutic interventions.

49, XXXYY is a rare form of sex chromosomal aneuploidy that has been reported in 11 cases worldwide. The parental origin of the extra sex chromosomes and the specific clinical features of this condition remain unclear. We recruited a case with 49, XXXYY and performed genome-wide copy number variation analysis using next-generation sequencing. In addition, the parental origin of the extra sex chromosomes was determined through short tandem repeats (STRs) locus genotyping. Furthermore, a comprehensive review and comparison of clinical phenotypes were conducted among 12 cases with 49, XXXYY. The patient exhibited a karyotype of 49, XXXYY without any mosaic patterns. No pathogenic microdeletions or microduplications (> 100 kb) were identified in autosomes 1-22. Analysis of the STR loci revealed that two of three X chromosomes originated from father. This suggests that the nondisjunction of chromosomes X and Y during stages I and II of meiotic spermatogenesis led to the production of an abnormal sperm with XXYY. Subsequently, fertilization of a normal oocyte with this abnormal sperm resulted in an abnormal zygote with pentasomy XXXYY. The main clinical features observed in these cases included varying degrees of mental retardation, minor facial dysmorphology, and gonadal or endocrine abnormalities. In conclusion, 49, XXXYY is a rare chromosomal disorder characterized by mental retardation and facial dysmorphology. Nondisjunction of chromosomes X and Y during stages I and II of meiotic spermatogenesis is a critical factor contributing to the development of this abnormal karyotype.

Background: A growing number of studies are exploring the association between HOTAIR rs920778 polymorphisms and cancer risk, but to date, there has been controversy and uncertainty. Preliminary evidence suggests that this polymorphism may influence cancer susceptibility, particularly in Asian populations and specific cancer types such as cervical cancer (CC) and breast cancer (BC). We therefore conducted an updated meta-analysis to accurately assess the association of the HOTAIR rs920778 polymorphism with cancer risk. Method: Comprehensive literature searches were performed in PubMed, Embase, and Web of Science up to September 8, 2023. Inclusion criteria included case-control studies with allele frequency data for both cases and controls. A total of 29 case-control studies were selected for quantitative analysis. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using Stata software (Version 11) to evaluate the association between the rs920778 polymorphism and cancer risk. Heterogeneity and publication bias were assessed using chi-square tests, I ² statistics, and funnel plots with Egger's test. Results: Our analysis of the results found a significant association between the rs920778 polymorphism and cancer susceptibility. In Asian populations, all five genetic models of the rs920778 polymorphism have been shown to increase overall cancer susceptibility. At the same time, we performed stratified analyses based on cancer type and found that all genetic models revealed significantly increased susceptibility to CC in Asian populations. Conversely, the heterozygote model of rs920778 demonstrated significantly reduced susceptibility to BC, with consistent effects across racial groups. Conclusions: Our meta-analysis demonstrated that the HOTAIR rs920778 polymorphism may be a risk factor for cancer but may serve as a protective factor for BC. Future studies require larger sample sizes and gene function analysis, suggesting that the rs920778 polymorphism could serve as a genetic biomarker to guide targeted therapies or cancer screening.

Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental conditions with complex genetic etiologies. Recent advances in whole exome sequencing (WES) have enabled comprehensive detection of clinically relevant variants, particularly single-nucleotide variations (SNVs) and InDels, in ASD genetic diagnostics. Here, we performed WES on 50 Chinese children with ASD who tested negative for copy number variants (CNVs). The analysis achieved a diagnostic yield of 10% (5/50 cases). All SNVs and InDels were loss-of-function (LOF) and were slightly more frequent among females (male vs. female: 9.3% vs. 14.3%). A total of five causative genes (PRODH9, PTEN, DEPDC5, SATB2, and CYFIP1) were identified in this study. Variants in ASD-associated genes (CHD8, FOXP1, and SHANK1) and genes linked to other neurodevelopmental disorders (CDH15, GATAD2B, and SHROOM4) were also detected. Despite the small sample size, our findings contribute partially to the dataset on the phenotype and genetic etiology of ASD and underscore WES as a critical tool for elucidating genetic etiologies in CNV-negative ASD cohorts.

Background: Coagulation system abnormalities contribute to clinical manifestations in preeclampsia (PE), but the mechanisms of coagulation and fibrinolysis in PE are unclear. Methods: We utilized the Gene Expression Omnibus (GEO) database to obtain the GSE10588 training set and GSE54618 validation set. From GeneCards, we extracted 514 coagulation and fibrinolysis-related genes (CFRGs). Differential expression analysis identified 1521 DEGs in the GSE10588 training set. WGCNA revealed the salmon module (778 genes) as the key module. LASSO and SVM-RFE methods identified four biomarkers (CYP19A1, C1QBP, GHR, and PSMA3) for a diagnostic model. GSEA was performed on the biomarkers. Immune cell infiltration and therapeutic agents for the biomarkers were analyzed. A circRNA-miRNA-mRNA network was constructed. Results: The salmon module showed the highest correlation with PE and normal samples. The diagnostic model comprised CYP19A1, C1QBP, GHR, and PSMA3. Immune cell analysis revealed significant differences, including type 2 T helper cells and regulatory T cells. C1QBP correlated positively with effector memory CD4 T cells, while PSMA3 had a negative correlation with CD56dim natural killer cells. Sixty-one potential therapeutic agents were predicted, as well as n circRNA-miRNA-mRNA network composed of 73 nodes and 88 edges. Conclusion: Our bioinformatic analysis resulted in a diagnostic model (CYP19A1, C1QBP, GHR, and PSMA3) for PE related to coagulation and fibrinolysis. We also conducted immune microenvironment and drug sensitivity analyses, providing insights into PE diagnosis and treatment.

Background: Hypospadias is one of the most common male congenital external genital malformation anomalies with unclear and multifactorial etiology. Our study aims to investigate whether IRX6 rs6499755 and HAAO rs3816183 polymorphisms are susceptible to hypospadias in Chinese Northern Han. Methods: We enrolled 113 patients with hypospadias and 182 healthy controls in the case-control study. Genotyping of single nucleotide polymorphisms (SNPs) was performed using High Resolution Melting (HRM). 113 hypospadias cases were further divided into anterior, middle and posterior subgroups for analysis. In addition, we performed a meta-analysis to evaluate the relationship in multiple populations. Results: The risk allele [C] of IRX6 rs6499755 was significantly associated with susceptibility to general hypospadias (OR = 1.547, p=0.01), anterior hypospadias (OR = 3.579, p=0.003) and posterior hypospadias (OR = 1.737, p=0.005). Besides, CC genotype carriers showed an increased risk of hypospadias compared with CT + TT carriers (OR = 1.832, p=0.026). The risk allele [T] of HAAO rs3816183 was associated with susceptibility to anterior/middle hypospadias (OR = 1.775, p=0.046). GMDR analysis revealed a significant interaction between IRX6 rs6499755 and HAAO rs3816183 in the risk of hypospadias (cross-validation consistency = 10/10, testing balanced accuracy = 0.6065, p=0.0010). The results of meta-analysis (including 3789 cases and 9241 controls) indicated that IRX6 rs6499755 and HAAO rs3816183 were significantly associated with hypospadias (both p < 0.00001). Conclusions: IRX6 rs6499755 and HAAO rs3816183 polymorphisms were associated with hypospadias in Chinese Northern Han, and there is a potential interaction between IRX6 rs6499755 and HAAO rs3816183 affecting the risk of hypospadias. The meta-analysis supported the hypothesis that IRX6 rs6499755 and HAAO rs3816183 were the susceptibility loci for hypospadias. Further research is needed to clarify their pathogenic mechanisms.

Background: This study aims to investigate the mutation spectrum of β-thalassemia in Fujian Province, China, and to comprehensively analyze the correlation between age, gender, genotype, and hematological parameters in carriers of β-thalassemia. Methods: Genotypes of 10,350 subjects suspected of having thalassemia were analyzed using reverse dot blotting (RDB) or β-globin gene sequencing. Their hematological indices were analyzed by genotype, gender, and age. Results: Among the subjects, 1214 (11.73%) were identified as β-thalassemia carriers. The prevalent genotypes included IVS-II-654 (C > T)/N (37.56%), CD 41-42 (-TTCT)/N (30.72%), CD 17 (A > T)/N (9.64%), -28 (A > G)/N (7.00%), CD 27-28 (+C)/N (3.21%), and CD 26 (GAG > AAG)/N (3.05%). Two rare mutations, Cap+22 (G > A) and IVS-II-806 (G > C), were detected, with the latter being part of a double heterozygous condition with hemoglobin (Hb) New York, compound -α4.2/αα, and Hb Q Thailand, marking the first report in Chinese individuals. Hematological analysis revealed that the CD 26 group exhibited higher levels of Hb, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) compared to the β⁰ and β⁺ groups (p < 0.05). Within the β⁺ group, individuals with -28 (A > G)/N showed significantly higher Hb, MCV, and MCH levels compared to those with IVS-II-654 (C > T)/N. Adult males had higher Hb levels than adult females, and adult patients generally had higher MCV and MCH levels than minors (p < 0.05). Conclusion: This study represents the first comprehensive molecular epidemiological investigation and hematological analysis of β-thalassemia in Fujian Province, providing support for the optimization of prevention and control strategies for thalassemia.