Genetic testing and molecular biomarkers最新文献

Background: We aim to investigate the possible causal association between Hashimoto's thyroiditis (HT) and rheumatoid arthritis (RA) using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted to evaluate the causal association between HT and RA. We obtained summary statistics data from two extensive genome-wide association studies (GWAS) comprising 15,654 cases of HT and 14,361 cases of RA. The primary effect estimate utilized in this study was the inverse-variance weighted (IVW) method. To ensure the reliability and stability of the results, we employed several additional methods for testing, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. Results: Our study revealed compelling evidence of bidirectional causality between HT and RA. When HT was considered as an exposure factor and RA was considered as an outcome factor, this study revealed a positive correlation between HT and RA (IVW: odds ratio [OR] = 2.4546, 95% confidence interval [CI], 1.1473-5.2512; p = 0.0207). Conversely, when we examined RA as the exposure factor and HT as the outcome factor, we still found a positive correlation between them (IVW: OR = 1.2113, 95% CI, 1.1248-1.3044; p = 3.9478 × 10^-7). Conclusions: According to our research findings, there exists a bidirectional positive causal relationship between HT and RA among European populations. This implies that individuals with HT have an elevated risk of developing RA, and conversely, individuals with RA have an increased risk of developing HT.

Background: Micro RNAs are new diagnostic markers and therapeutic targets in breast cancer research. miR-107 and miR-126 have been reported to be linked with the pathogenesis of breast cancer. The present study investigates the levels of expression of miR-107 and miR-126 in patients with breast cancer to find their correlation with the risk of breast cancer in Amritsar, Punjab, Northwest India. Material and Methods: In total, 200 subjects, 100 patients with breast cancer and 100 controls, were enrolled to screen the expression of miR-107 and miR-126 using quantitative reverse transcription polymerase chain reaction (RT-PCR) technique. The Livak method (2^-ΔΔCt) was used to calculate the fold change of the expression of micro RNAs. Student t-test was used to calculate the significant change in the expression of miRNAs in patients as compared with controls. Spearman rank correlation coefficient and ROC were conducted. The value of p < 0.05 was considered to indicate a statistically significant difference. Results: miR-107 was downregulated in patients with breast cancer as compared with controls (fold change = 0.467; p = 0.114) but not statistically significant. The expression of miR-126 was found to be 5.37 times elevated in patients with breast cancer, specifically in stage I and stage III patients (p = 0.009), compared with controls, which may indicate its oncogenic activity. The ROC analyses revealed that miR-126 could be a potential diagnostic marker. In conclusion oncogenic behavior of miR-126 is suggestive of its role in pathogenesis in patients with breast cancer.

Background: Sepsis is a complex clinical syndrome caused by a dysregulated host immune response to infection. This study aimed to identify a competing endogenous RNA (ceRNA) network that can greatly contribute to understanding the pathophysiological process of sepsis and determining sepsis biomarkers. Methods: The GSE100159, GSE65682, GSE167363, and GSE94717 datasets were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene coexpression network analysis was performed to find modules possibly involved in sepsis. A long noncoding RNA-microRNA-messenger RNA (lncRNA-miRNA-mRNA) network was constructed based on the findings. Single-cell analysis was performed. Human umbilical vein endothelial cells were treated with lipopolysaccharide (LPS) to create an in vitro model of sepsis for network verification. Reverse transcription-polymerase chain reaction, fluorescence in situ hybridization, and luciferase reporter genes were used to verify the bioinformatic analysis. Result: By integrating data from three GEO datasets, we successfully constructed a ceRNA network containing 18 lncRNAs, 7 miRNAs, and 94 mRNAs based on the ceRNA hypothesis. The lncRNA ZFAS1 was found to be highly expressed in LPS-stimulated endothelial cells and may thus play a role in endothelial cell injury. Univariate and multivariate Cox analyses showed that only SLC26A6 was an independent predictor of prognosis in sepsis. Overall, our findings indicated that the ZFAS1/hsa-miR-449c-5p/SLC26A6 ceRNA regulatory axis may play a role in the progression of sepsis. Conclusion: The sepsis ceRNA network, especially the ZFAS1/hsa-miR-449c-5p/SLC26A6 regulatory axis, is expected to reveal potential biomarkers and therapeutic targets for sepsis management.

Objective: This study aims to identify causal variants associated with vitiligo in an expanded region of 10q22.1. Materials and Methods: We conducted a fine-scale deep analysis of the expanded 10q22.1 region using in a large genome-wide association studies dataset consisting of 1117 cases and 1701 controls through imputation. We selected five nominal coding single nucleotide polymorphisms (SNPs) located in SLC29A3 and CDH23 and genotyped them in an independent cohort of 2479 cases and 2451 controls in a Chinese Han population cohort using the Sequenom MassArray iPLEX1 system. Results: A missense SNP in SLC29A3, rs2252996, showed strong evidence of association with vitiligo (p = 1.34 × 10^-8, odds ratio [OR] = 0.82). Three synonymous SNPs (rs1084004 in SLC29A3; rs12218559 and rs10999978 in CDH23) provided suggestive evidence of association for vitiligo (p = 1.69 × 10^-6, OR = 0.84; p = 9.47 × 10^-5, OR = 1.18; p = 6.90 × 10^-4, OR = 1.16, respectively). Stepwise conditional analyses identified two significant independent disease-associated signals from the four SNPs (both p < 0.05; both D' = 0.03; and r² = 0.00). Conclusion: The study identifies four genetic coding variants in SLC29A3 and CDH23 on 10q22.1 that may contribute to vitiligo susceptibility with one missense variant affecting disease subphenotypes. The presence of multiple genetic variants underscores their significant role in the genetic pathogenesis of the disease.

Background: The extracellular matrix (ECM) glycoprotein changes are associated with the pathogenesis and complications of atherosclerosis, leading to acute coronary syndrome (ACS). Tenascin-C (TNC), an ECM protein, has been implemented in the pathogenesis, diagnosis, and prognosis of patients with cardiovascular disease. Aim: The study aimed to compare the genetic variants of the TNC gene (rs13321, rs2104772, and rs12347433) between South Indians with ACS and healthy participants. Materials and Methods: This case-control study recruited 150 ACS patients as cases and 150 healthy participants as controls. TNC genotyping was performed using TaqMan 5'-exonuclease allele discrimination assay. Serum TNC levels were measured by enzyme-linked immunosorbent assay. Results: Serum TNC levels were significantly higher in cases compared with controls. No significant difference was observed in allele and genotype frequencies of rs13321, rs2104772, and rs12347433 between cases and controls, which was confirmed by dominant, recessive, codominant, and homozygotic genetic models. The patients with heterozygous genotypes of rs13321, rs2104772, and rs12347433 had significantly lower serum TNC levels than patients with respective homozygous genotypes. Haplotype analyses revealed that the C-T-A haplotype in the block of rs13321-rs12347433-rs2104772 was associated with lower ACS risk (OR = 0.33, 95% CI: 0.15 - 0.75; p = 0.005). Also, the C-T-T and G-T-A haplotypes of the TNC gene were associated with higher and lower serum TNC levels, respectively. Conclusion: Our study demonstrated no genetic association between single nucleotide polymorphisms of the TNC gene and ACS risk; however, the C-T-A haplotype of the TNC gene might be associated with reduced ACS risk in South Indians.

Background: Ferroptosis is associated with tumor development; however, its contribution to radioresistant head and neck cancer (HNC) remains unclear. In this study, we used bioinformatics analysis and in vitro testing to explore ferroptosis-related genes associated with HNCs radiosensitivity. Materials and Methods: GSE9714, GSE90761, and The Cancer Genome Atlas (TCGA) datasets were searched to identify ferroptosis-related differentially expressed genes between radioresistant and radiosensitive HNCs or radiation-treated and nonradiation-treated HNCs. A protein-protein interaction analysis on identified hub genes was then performed. Receiver operating characteristic curves and Kaplan-Meier survival analysis were used to assess the diagnostic and prognostic potential of the hub genes. Cell counting kit-8, transwell assay, and flow cytometry were applied to examine the role of hub gene collagen type IV, alpha1 chain (COL4A1) on the proliferation, migration, invasion, and apoptosis of TU686 cells. Results: Hub genes MMP10, MMP1, COL4A1, IFI27, and INHBA showed diagnostic potential for HNC and were negatively correlated with overall survival and disease-free survival in the TCGA dataset. Also, IL-1B, IFI27, INHBA, and COL4A1 mRNA levels were significantly increased in TCGA patients with advanced clinical stages or receiving radiotherapy, whereas COL4A1, MMP10, and INHBA expressions were negatively correlated with immune infiltration. Furthermore, the knockdown of COL4A1 inhibited cell proliferation, migration, and invasion while promoting apoptosis in TU686 cells. Conclusion: Ferroptosis-related hub genes, such as COL4A1, are potential diagnostic and prognostic indicators as well as therapeutic targets for HNC.

Aim: The matrix metalloproteinases (MMPs) inhibit tissue inhibitors of metalloproteinases (TIMPs), playing a notable role in various biological processes, and mutations in TIMP2 genes impact a variety of urinary cancers. In this study, we analyze and evaluate the potential involvement of the TIMP2 418 G/C and MMP gene polymorphism in the etiology of urinary cancer. Methodology: For suitable case-control studies, a literature search was undertaken from various database sources such as PubMed, EMBASE, and Google Scholar. Incorporated into the analysis were case-control or cohort studies that documented the correlation between TIMP2 418 G/C and urological cancers. MetaGenyo served as the tool for conducting the meta-analysis, employing a fixed-effects model. The collective odds ratios, along with their corresponding 95% confidence intervals, were calculated and presented to assess the robustness of the observed associations. Results: A total of seven studies involving controls and cases out of recorded 1265 controls and 1154 cases were analyzed to ascertain the significant association of the TIMP2 gene with urologic cancer. No statistically significant correlation was observed between allelic, recessive, dominant, and overdominant models for the genetic variant under investigation. A 95% confidence interval (CI) and odds ratio (OR) were computed for each model, considering p-values <0.05. The OR and 95% CI for the allelic model were 0.99 and 0.77-1.27, respectively, whereas the respective values were 1.00 and 0.76-1.32 for the recessive model. In the dominant contrast model, OR and 95% CI were 1.09 and 0.62-1.90, while the same were 0.93 and 0.77-1.12 for the overdominant model. A funnel plot was used to reanalyze and detect the results as statically satisfactory. Conclusions: As a result of the data obtained, the TIMP2 gene polymorphism does not correlate statistically with cancer risk. The significance of this finding can only be confirmed using a large population, extensive epidemiological research, a comprehensive survey, and a better understanding of the molecular pathways associated.

Background: At present, numerous clinical studies suggest a correlation between inflammatory bowel disease (IBD) and skin cancer. However, some articles present differing views that IBD does not increase the risk of skin cancer. The presence of potential reverse causality and residual confounding is inherent in conventional observational studies. Thus, this study used a two-sample Mendelian randomization (MR) study design to estimate the causal effect of IBD on the risk of skin cancer, including cutaneous malignant melanoma (CMM, also named melanoma skin cancer) and nonmelanoma skin cancer (NMSC). Design: In this study, a two-sample MR analysis was used to estimate the causal effect of IBD on skin cancer outcomes. The inverse-variance weighted (IVW) method was used as the main MR analysis, with multiple sensitivity analyses conducted to assess the robustness of findings. Results: In examining the association between IBD and NMSC, all p-values of the IVW methods were found to be <0.05, providing evidence for a causal effect of IBD on an increased risk of NMSC. However, IVW for IBD on CMM yielded p-values >0.05, indicating no causal relationship between IBD and CMM. These findings were consistent across other MR methods, with no evidence of pleiotropy or heterogeneity. Sensitivity analyses confirmed the robustness of our results. Conclusion: Using MR analysis, we found evidence for a causal effect of genetic liability for IBD on an increased risk of NMSC. However, our study did not find sufficient evidence to support a significant impact of IBD on CMM outcomes.

Introduction: Microtia is the second most common maxillofacial birth defect worldwide. However, the involvement of long non-coding RNAs (lncRNAs) in isolated microtia is not well understood. This study aimed at identifying lncRNAs that regulate the expression of genes associated with isolated microtia. Methods: We used our microarray data to analyze the expression pattern of lncRNA in the auricular cartilage tissues from 10 patients diagnosed with isolated microtia, alongside 15 control subjects. Five lncRNAs were chosen for validation using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: We identified 4651 differentially expressed lncRNAs in the auricular cartilage from patients with isolated microtia. By Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway (GO/KEGG) analysis, we identified 27 differentially expressed genes enriched in pathways associated with microtia. In addition, we predicted 9 differentially expressed genes as potential cis-acting targets of 12 differentially expressed lncRNAs. Our findings by qRT-PCR demonstrate significantly elevated expression levels of ZFAS1 and DAB1-AS1, whereas ADIRF-AS1, HOTAIRM1, and EPB41L4A-AS1 exhibited significantly reduced expression levels in the auricular cartilage tissues of patients with isolated microtia. Conclusions: Our study sheds light on the potential involvement of lncRNAs in microtia and provides a basis for further investigation into their functional roles and underlying mechanisms.