RESUMEN
PURPOSE: Papillary thyroid carcinoma (PTC) represents the most common subtype of thyroid cancer (TC). This study was set out to explore the potential effect of CHD1L on PTC and type 2 diabetes mellitus (T2DM). METHODS: We searched for T2DM susceptibility genes through the GWAS database and obtained T2DM-related differentially expressed gene from the GEO database. The expression and clinical data of TC and normal samples were collated from the TCGA database. Receiver operating characteristic (ROC) curve analysis was subsequently applied to assess the sensitivity and specificity of the CHD1L for the diagnosis of PTC. The MCP-counter package in R language was then utilized to generate immune cell score to evaluate the relationship between CHD1L expression and immune cells. Then, we performed functional enrichment analysis of co-expressed genes and DEGs to determine significantly enriched GO terms and KEGG to predict the potential functions of CHD1L in PTC samples and T2DM adipose tissue. RESULTS: From two genes (ABCB9, CHD1L) were identified to be DEGs (p < 1 * 10-5) that exerted effects on survival (HR > 1, p < 0.05) in PTC and served as T2DM susceptibility genes. The gene expression matrix-based scoring of immunocytes suggested that PTC samples with high and low CHD1L expression presented with significant differences in the tumor microenvironment (TME). The enrichment analysis of CHD1L co-expressed genes and DEGs suggested that CHD1L was involved in multiple pathways to regulate the development of PTC. Among them, Kaposi sarcoma-associated herpesvirus infection, salmonella infection and TNF signaling pathways were highlighted as the three most relevant pathways. GSEA analysis, employed to analyze the genome dataset of PTC samples and T2DM adipose tissue presenting with high and low expression groups of CHD1L, suggests that these differential genes are related to chemokine signaling pathway, leukocyte transendothelial migration and TCELL receptor signaling pathway. CONCLUSION: CHD1L may potentially serve as an early diagnostic biomarker for PTC, and a target of immunotherapy for PTC and T2DM.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Biología Computacional/métodos , ADN Helicasas/metabolismo , Proteínas de Unión al ADN/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Estudio de Asociación del Genoma Completo , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Biomarcadores de Tumor/genética , ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Estudios de Seguimiento , Humanos , Pronóstico , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Microambiente TumoralRESUMEN
Several previous studies have investigated whether the -160C/A epithelial cadherin promoter polymorphism confers an increased risk of diffuse gastric cancer (DGC), but conflicting results have been reported. To explore further the association of this polymorphism with DGC susceptibility, we performed an extensive search of relevant studies and conducted a meta-analysis to obtain a more precise estimate. We conducted a systematic literature search using the databases EMBASE, PubMed, and Web of Knowledge for reports published before August 2012 that met certain criteria. Information was carefully and independently extracted from all eligible publications by 2 of the authors. Twelve distinct data sets from 10 case-control studies were analyzed. They included 1115 cases of DGC and 2965 controls. Although none of the genotypes was associated with DGC risk, a slight trend of increased risk was found among A allele carriers [odds ratio (OR) = 1.237, 95% confidence interval (95%CI), 0.940-1.627], CA heterozygotes (OR = 1.229, 95%CI = 0.938-1.610), and AA homozygotes (OR = 1.146, 95%CI = 0.684-1.918). However, when the cases were stratified by ethnicity, a diverging trend occurred in AA homozygotes between the Asian group (OR = 0.710, 95%CI = 0.328-1.536) and its Caucasian counterpart (OR = 1.434, 95%CI = 0.657-3.131). Taken together, the summarized analyses of these case-control studies demonstrated that the -160A of the epithelial cadherin gene exhibited no significant association with susceptibility for DGC; however, the results suggested that it is a potential genetic risk factor in both Asians and Caucasians. Additional large-scale, well-designed studies are necessary to confirm whether AA homozygosity is a protective factor in Asians.