Genome-wide scanning for CHD1L gene in papillary thyroid carcinoma complicated with type 2 diabetes mellitus

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 (AU)

SMARCA4 promotes benign skin malignant transformation into melanoma through Adherens junction signal transduction

Purpose Melanoma is a malignant skin tumor, and its incidence is rising. To explore the specific differences in benign and malignant melanoma at the genetic level, we performed a series of bioinformatics analyses, including differential gene analysis, co-expression analysis, enrichment analysis, and regulatory prediction. Methods The microarray data of benign and malignant melanocytes were downloaded from GEO, and 1917 differential genes were obtained by differential analysis (p < 0.05). Weighted gene co-expression network analysis obtained three functional barrier modules. The essential genes of each module are SMARTA4, HECA, and C1R. Results The results of the enrichment analysis showed that the dysfunctional module gene was mainly associated with RNA splicing and Adherens junction. Through the pivotal analysis of ncRNA, it was found that miR-448, miR-152-3p, and miR-302b-3p essentially regulate three modules, which we consider to be critical regulators. In the pivot analysis of TF, more control modules include ARID3A, E2F1, E2F3, and E2F8. Conclusions We believe that the regulator (miR-448, miR-152-3p, miR-302b-3p) regulates the expression of the core gene SMARCA4, which in turn affects the signal transduction of the Adherens junction. It eventually leads to the deterioration of benign skin spasms into melanoma (AU)

Decreased expression of chromodomainhelicase DNA-binding protein 5 is an unfavorable prognostic marker in patients with primary gallbladder carcinoma

AIM: Chromodomain helicase DNA-binding protein 5 (CHD5) plays a role in normal neural development and in tumorigenesis of various human cancers. However, its role in primary gallbladder carcinoma (PGC) is still unclear. The aim of this study was to investigate CHD5 expression in PGC and its clinical significance. METHODS: CHD5 mRNA and protein expression in 120 PGC and 20 normal gallbladder specimens was determined by quantitative reverse transcription-polymerase chain reaction (QRT-PCR) and Western blotting analysis, respectively. RESULTS: The expression levels of CHD5 mRNA and protein in PGC tissues were both significantly lower than those in the normal epithelium of the gallbladder (mRNA: P = 0.006; protein: P = 0.01). CHD5 mRNA expression was closely correlated with its protein expression (r = 0.8; P < 0.001). Additionally, the low expression of CHD5 protein was significantly associated with high pathologic T stage (P = 0.01) and clinical stage (P = 0.008), and advanced histologic grade (P = 0.009). The expression levels of CHD5 protein in PGC tissues with positive nodal metastasis were also significantly lower than those without (P = 0.01). Survival analysis showed that low CHD5 expression was associated with shorter disease-free (P = 0.01) and overall survival (P = 0.008) compared to those with high CHD5 expression in PGC patients. Furthermore, multivariate analyses showed that the decreased expression of CHD5 was an independent prognostic marker for both unfavorable disease-free (P = 0.01) and overall survival (P = 0.006). CONCLUSION: CHD5 may be involved in carcinogenesis of PGC and its down-regulation may be significantly correlated with unfavorable clinicopathologic features including poor overall and disease-free survival in patients (AU)

An insight into the genetics of type 1 Diabetes

La diabetes tipo 1 (T1D) es una enfermedad compleja causada por ladestrucción autoinmune de las células beta del páncreas, fruto de la interacción entre factores genéticos y ambientales. A pesar de los enormes avances en el estudio de la T1D, los mecanismos etiológicos de la enfermedad ylos factores genéticos y ambientales implicados en la misma siguen siendoen parte desconocidos. La investigación en el campo de la genética de la T1D abarca más detreinta años y se han descubierto hasta 40 regiones cromosómicas relacionadas con la susceptibilidad a T1D. Algunas de ellas, como la correspondiente al HLA o al gen de la insulina, se han establecido claramente comofactores de riesgo, mientras que en otras se necesita confirmar resultadospreliminares. En este texto revisaremos algunos de estos genes de susceptibilidad: los alelos del MHC de clase II, el gen de la insulina, CTLA4,PTPN22, IL2 y la subunidad de su receptor IL2RA, la helicasa IFIH1/MDA5,el bloque CAPSL-IL7R, la lectina CLEC16A, el factor de transcripción de larespuesta Th1 STAT4 y la tirosin-fosfatasa PTPN2 (AU)

Type 1 Diabetes (T1D) is a complex trait caused by T-cell mediatedautoimmune destruction of islet beta cells in the pancreas, resulting of theinteraction between genetic and environmental factors. Despite enormousadvances in the study of T1D, the aethiologic mechanisms of this diseaseand the genetic and environmental factors involved remain not fully determined. Research in the field of T1D genetics spans now for more than thirtyyears and up to 40 chromosomic regions associated with T1D susceptibility have been reported. Some of these, namely the HLA region or theinsulin gene, are clearly established as risk factors while others need morestudy to confirm preliminary results. In this text we will review some ofthe main susceptibility genes currently accepted for T1D: the MHC classII alleles, the insulin gene, CTLA4, PTPN22, IL2 and its receptor subunitIL2RA, the helicase IFIH1/MDA5, the CAPSL-IL7R block, the lectinCLEC16A, the Th1 transcription factor STAT4, and the tyrosine phosphatase PTPN2 (AU)