Dataset Information

Predictive and prognostic molecular markers for cholangiocarcinoma in Han Chinese population.

ABSTRACT: Cholangiocarcinoma (CCA) is the most common malignant heterogeneous polygenetic carcinoma with a high incidence in Asia. Most patients would die within 1 year after diagnosis and the 5 year survival rate is less than 10-20% worldwide. Single nucleotide polymorphisms (SNPs) in genes regulate telomere maintenance, mitosis, and inflammation, and may help predict individual susceptibility to certain drugs, environmental factor, and risks to particular diseases. The gene-gene interaction and the regulation of SNPs have not been assessed extensively in CCA. According to our previous study, the GRB2-associated-binding protein (Gab1) gene rs3805246 (X(2) =5.015, P=0.025, OR=0.531, 95% CI 0.304-0.928) and epidermal growth factor receptor (EGFR) gene rs2007000 (X(2) =7.934, P=0.005, OR=2.148, 95% CI 1.255-3.675) presented significant difference between CCA patients and controls. This study conducted a population-based analysis using 225 CCA cases (153 biliary tract cancer patients and 72 gall bladder cancer patients) to assess the association between SNPs and progression of CCA patients, including the overall survival and the prognosis analysis. Results showed that an increased susceptibility of BTC was significantly associated with SNP loci distribution frequency in EGFR rs2107000 (X(2) =7.934, P=0.005, OR=2.148, 95% CI 1.255-3.675). Furthermore, multivariate factor regression analysis represented cholelithiasis medical history of BTC patients can be an effective evaluation criteria of BTC susceptibility in early stage. This study also assessed the relationship between these genotypic polymorphisms and clinicopathologic data, including tumor differentiation stage and overall survival. This is the first study identifying that EGFR polymorphisms are associated with BTC and EGFR rs2017000 polymorphisms may be an important survival predictor in BTC patients.

SUBMITTER: Meng L

PROVIDER: S-EPMC4612998 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Predictive and prognostic molecular markers for cholangiocarcinoma in Han Chinese population.

Meng Lingqin L Tian Zhong Z Wang Yong Y Liu Yuan Y Liu Jingang J

International journal of clinical and experimental medicine 20150815 8

Cholangiocarcinoma (CCA) is the most common malignant heterogeneous polygenetic carcinoma with a high incidence in Asia. Most patients would die within 1 year after diagnosis and the 5 year survival rate is less than 10-20% worldwide. Single nucleotide polymorphisms (SNPs) in genes regulate telomere maintenance, mitosis, and inflammation, and may help predict individual susceptibility to certain drugs, environmental factor, and risks to particular diseases. The gene-gene interaction and the regu ...[more]

PMID: 26550313

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Project description:Psoriasis is a chronic inflammatory skin disease related to immune, whose complexity of molecular mechanisms is still not fully clear. RNA sequencing has been widely applied in various fields including biological medicine. According to the bioinformatics analysis of differential genes, biomarkers and drug targets have been discovered for the diagnosis and treatment of diseases. Besides, the pathological mechanisms of disease and functions of gene can be evaluated. In the present study, we report the application of RNA sequencing in skin tissues from psoriatic and healthy persons. By obtaining 2139 differential expressed genes (DEGs), 208 significantly differential GO terms and 44 significantly differential pathways were generated. We found that the functions of DEGs were mainly related to cell cycle, inflammatory, virus, immune response and metabolic process.The major pathways included cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway, cell cycle, metabolic pathways, ribosome, peroxisome, steroid biosynthesis and biosynthesis of unsaturated fatty acids. Furthermore, co-expression network was constructed to identify core genes and relations between genes. we considered genes with high values of degree and k-core difference in the co-expression network as core genes, such as IFNG, IL26, TLR3, PRKCQ, TLR4, CD274, CDK1 and IL17A. We chose CD274, an important immune checkpoint, to evaluate its regulatory mechanisms. Candidate genes related to CD274 were evaluated by the co-expression network analysis, and the relations between CD274 and candidate genes were validated in epidermal keratinocytes. Finally, IFNG and CDK1 inhibitor (indirubin) were found increasing the expression levels of CD274. In addition, indirubin was confirmed to attenuate mouse psoriasis-like skin lesion with the mechanisms related to CD274. In conclusion, this study provides us a comprehensive transcriptome analysis method on psoriasis to identify core genes and explore the important regulatory functions of genes.

Dataset Information

Predictive and prognostic molecular markers for cholangiocarcinoma in Han Chinese population.

Publications

Predictive and prognostic molecular markers for cholangiocarcinoma in Han Chinese population.

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