Background. Lymphocyte antigen 6 complex, locus E (LY6E) is abnormally expressed in several cancers and is associated with poor outcomes. However, the biological role of LY6E in colorectal cancer (CRC) remains largely unknown. Hence, we aimed to evaluate the expression levels, prognostic value, biological functions, and immune effects of LY6E via pan-cancer and CRC analyses using multiple databases. Methods. We analyzed the expression pattern of LY6E in various cancers. The prognostic value of LY6E expression was identified using the Kaplan–Meier analysis and the Cox regression models. We used gene set enrichment analysis (GSEA) to identify the potential functions of LY6E. Correlations between the LY6E expression and various factors, including LY6E methylation level, copy number variation (CNV), microsatellite instability (MSI), and immune checkpoint genes, were also analyzed. The levels of LY6E expression and immune infiltration were analyzed using CIBERSORT. We constructed a regulatory network that was in compliance with the competing endogenous RNA (ceRNA) hypothesis. A ceRNA expression-based nomogram was established. Real-time PCR (qRT-PCR) was applied to validate the expression of LY6E-related ceRNA in CRC cell lines. Results. LY6E is overexpressed in several tumor types, including CRC, and patients with high expression levels of LY6E have a poor prognosis. The Kaplan–Meier analysis and Cox regression analysis showed that LY6E could be considered a favorable prognostic factor in TCGA and GEO cohort. The results of GSEA showed that high LY6E expression levels were associated with immune-related pathways, such as those involved in antigen processing and presentation and the intestinal immune network for IgA production. Six methylation sites of LY6E that were associated with prognostic survival were screened. Moreover, the high levels of LY6E expression were correlated with copy number gain, microsatellite instability high, and immunotherapy response. The results of CIBERSORT analysis demonstrated that the LY6E expression levels were correlated with the infiltration of multiple immune cells, especially T cells. Then, we constructed a ceRNA network (LINC00963/miR-92a-3p/LY6E) and validated it using qRT-PCR. A predictive ceRNA-based nomogram was established and validated. Conclusion. The oncogenic LY6E may serve as a promising marker for the diagnosis and treatment of CRC.
BackgroundA growing number of studies have implicated that gut microbial abundance and metabolite concentration alterations are associated with celiac disease (CD). However, the causal relationship underlying these associations is unclear. Here, we used Mendelian randomization (MR) to reveal the causal effect of gut microbiota and metabolites on CD.MethodsGenome-wide association study (GWAS) summary-level data for gut microbiota, metabolites, and CD were extracted from published GWASs. Causal bacterial taxa and metabolites for CD were determined by two-sample MR analyses. The robustness of the results was assessed with sensitivity analyses. Finally, reverse causality was investigated with a reverse MR analysis.ResultsGenetically, increased genus Bifidobacterium was potentially associated with higher CD risk (odds ratio [OR] = 1.447, 95% confidence interval [CI]: 1.054–1.988, p = 0.022) while phylum Lentisphaerae (OR = 0.798, 95% CI: 0.648–0.983, p = 0.034) and genus Coprobacter (OR = 0.683, 95% CI: 0.531–0.880, p = 0.003) were related to lower CD risk. Moreover, there were suggestive associations between CD and the following seven metabolites: 1-oleoylglycerophosphoethanolamine, 1-palmitoylglycerophosphoethanolamine, 1,6-anhydroglucose, phenylacetylglutamine, tryptophan betaine, 10-undecenoate, and tyrosine. Sensitivity analyses deemed the results reliable without pleiotropy.ConclusionWe investigated the causal relationships between gut microbiota, metabolites, and CD with two-sample MR. Our findings suggest several novel potential therapeutic targets for CD treatment. Further understanding of the underlying mechanism may provide insights into CD pathogenesis.
Ulcerative colitis (UC) is a progressive intestine inflammatory disease that is prone to recur. Herein, we utilize microarray technology and bioinformatics to reveal the underlying pathogenesis of UC and provide novel markers. Colonic biopsies were taken from eight UC patients and eight healthy controls. Three differentially expressed miRNAs (DEMIs) and 264 differentially expressed genes (DEGs) were screened using mRNA and miRNA microarray. Most DEGs were significantly associated with immune response and were markedly enriched in the IL-17 signaling pathway. Among the target genes of DEMIs, PHLPP2 overlapped with DEGs and the downregulation of PHLPP2 group was mainly involved in the epithelial–mesenchymal transition. PHLPP2 was downregulated in UC patients, which was validated in 5 GEO datasets and qRT-PCR. The ROC curve demonstrated that PHLPP2 has a perfect ability to distinguish UC patients from healthy controls. Moreover, PHLPP2 was low expression in patients with active UC. CIBERSORT algorithm indicated that the abundance of gamma delta T cells ( P = 0.04 ), M0 macrophages ( P = 0.01 ), and activated mast cells ( P < 0.01 ) was significantly greater than that of the control group. The Spearman correlation analysis showed that PHLPP2 was positively correlated with the proportion of activated NK cells ( rho = 0.62 , P = 0.013 ) and Tregs ( rho = 0.55 , P = 0.03 ), but negatively correlated with those of activated mast cells ( rho = − 0.8 , P < 0.01 ) and macrophages ( rho = − 0.73 , P < 0.01 ). These results indicate that PHLPP2 is associated with immune cells in the pathogenesis of UC, as well as provide new prospects and future directions of investigation.
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