Background: The epithelial-mesenchymal transition (EMT) plays a pivotal role in various physiological processes, such as embryonic development, tissue morphogenesis, and wound healing. EMT also plays an important role in cancer invasion, metastasis, and chemoresistance. Additionally, EMT is partially responsible for chemoresistance in colorectal cancer (CRC). The aim of this research is to develop an EMT-based prognostic signature in CRC. Methods: RNA-seq and microarray data, together with clinical information, were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. A total of 244 differentially expressed EMT-related genes (ERGs) were obtained by comparing the expression between normal and tumor tissues. An EMT-related signature of 11 genes was identified as crucially related to the overall survival (OS) of patients through univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO), and Cox regression analysis. Finally, we established a clinical nomogram to predict the survival possibility of CRC patients by integrating clinical characteristics and the EMT-related gene signature. Results: Two hundred and forty-four differentially expressed ERGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that EMT-related signaling pathway genes were highly related to CRC. Kaplan-Meier analysis revealed that the 11-EMT signature could significantly distinguish high- and low-risk patients in both TCGA and GEO CRC cohorts. In addition, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusion: We developed a novel EMT-related gene signature for the prognosis prediction of CRC patients, which could improve the individualized outcome prediction in CRC.

Background/Objective: This study aimed to investigate the causal relationship between urate level and female infertility using Mendelian randomization (MR) analysis. Methods: To identify instrumental variables, we selected independent genetic loci associated with serum urate levels in individuals of European ancestry, utilizing data from large-scale genome-wide association studies (GWAS). The GWAS dataset included information on serum urate levels from 288,649 CKDGen participants. Female infertility data, including different etiologic classifications, consisted of 13,142 female infertility patients and 107,564 controls. We employed four MR methods, namely inverse variance weighted (IVW), MR-Egger, weighted median, and weighted model, to investigate the causal relationship between urate levels and female infertility. The Cochran Q-test was used to assess heterogeneity among single nucleotide polymorphisms (SNPs), and the MR-Egger intercept test was employed to evaluate the presence of horizontal pleiotropy. Additionally, a “leave-one-out” sensitivity analysis was conducted to examine the influence of individual SNPs on the MR study. Results: The IVW analysis demonstrated that elevated serum urate levels increased the risk of female infertility (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07–1.33). Furthermore, serum urate levels were found to be associated with infertility due to cervical, vaginal, or other unknown causes (OR = 1.16, 95% CI: 1.06–1.26), also confirmed by other methods. Heterogeneity among instrumental variables was assessed using Cochran’s Q-test (p < 0.05), so a random-effects IVW approach was employed in the effects model. The MR-Egger intercept test indicated no presence of horizontal pleiotropy. A “leave-one-out” sensitivity analysis was conducted, demonstrating that no individual SNP had a substantial impact on the overall findings. Conclusions: In the European population, the urate level is significantly and causally associated with an increased risk of female infertility.

Background: Based on research evidence, bone mineral density(BMD) is closely related to the occurrence of osteoporosis and fractures, and tea intake in daily diet has an important impact on bone density changes. However, the inherent relationship between them is not clear. We adopted a two-sample Mendelian randomization (MR) method to evaluate the causal effect of tea intake on bone density and further explore whether it has specificity in different age groups. Methods： Analyzed meta-data from genome-wide association studies (GWAS) on tea consumption. Used single-nucleotide polymorphisms (SNPs) closely associated with tea consumption as instrumental variables (IVs) for a two-sample Mendelian randomization, the MR-Egger, IVW, Weighted median, Weighted mode methods were used to assess the causal analysis of tea intake between BMD at different ages. Result: Including 31 single nucleotide polymorphisms as instrumental variables. According to the results of inverse variance weighting (IVW), we found that tea intake had a positive causal effect on systemic BMD, but different age groups (0-15 years; 15-30 years; 30-45 years; 45-60 years; over 60 years) showed positive causality only in the 45-60 age range, with no significant statistical effect in other age groups. Evidence suggests that there is no genetic pleiotropic effect of tea intake on the causal effect of systemic BMD or between the five age groups (P> 0.05). In the IVW method, Cochran Q statistic and MR-Egger regression were used to calculate heterogeneity, and P > 0.05 indicates the absence of significant heterogeneity. Conclusion: The results of MR analysis showed that tea intake had a positive causal relationship on total body BMD, while in different age groups, tea intake only positively affected BMD in the 45–60 age group. This means that tea is beneficial for maintaining or increasing BMD in this age group, and may reduce the risk of osteoporosis and fracture.