Dataset Information

Genetic polymorphisms in MicroRNA-related genes as predictors of clinical outcomes in colorectal adenocarcinoma patients.

ABSTRACT: To evaluate the effects of single-nucleotide polymorphisms (SNP) in microRNA-related genes on clinical outcomes in patients with colorectal cancer (CRC) receiving first-line fluoropyrimidine-based chemotherapy.Forty-one SNPs in 26 microRNA-related genes were genotyped in 1,097 patients with CRC recruited at the University of Texas MD Anderson Cancer Center (Houston, TX). Patients were enrolled between 1990 and 2008 and last follow-up was in 2010. The associations between genotypes and recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) stratified by clinical stage were analyzed in 741 newly diagnosed patients (diagnosed within 1 year) and replicated the findings in an additional 356 patients.In patients with stage III disease, mir608: rs4919510 was associated with increased risk for both recurrence [HR, 2.72; 95% confidence interval (CI), 1.38-5.33] and death (HR, 3.53; 95%CI, 1.42-8.73). The associations were confirmed in the replication set, and the combined HRs for training and replication sets were 1.65 (95% CI, 1.13-2.41) for recurrence and 1.96 (95% CI, 1.19-3.21) for death, respectively. The mir219-1:rs213210 showed consistent association with death in the training set (HR, 3.86; 95% CI, 1.33-11.22), the replication set (HR, 3.33; 95% CI, 1.39-7.98), and combined data set (HR, 3.22; 95% CI, 1.70-6.10). In combined analysis of these two SNPs, patients carrying the variant genotypes at both sites exhibited a 5.6-fold increased risk of death.Genetic polymorphisms in the microRNA pathway may predict prognosis in patients with stage III CRC treated with fluoropyrimidine-based chemotherapy.

SUBMITTER: Lin M

PROVIDER: S-EPMC4141857 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic polymorphisms in MicroRNA-related genes as predictors of clinical outcomes in colorectal adenocarcinoma patients.

Lin Moubin M Gu Jian J Eng Cathy C Ellis Lee M LM Hildebrandt Michelle A MA Lin Jie J Huang Maosheng M Calin George A GA Calin George A GA Wang Dingzhi D Dubois Raymond N RN Hawk Ernest T ET Wu Xifeng X

Clinical cancer research : an official journal of the American Association for Cancer Research 20120601 14

<h4>Purpose</h4>To evaluate the effects of single-nucleotide polymorphisms (SNP) in microRNA-related genes on clinical outcomes in patients with colorectal cancer (CRC) receiving first-line fluoropyrimidine-based chemotherapy.<h4>Experimental design</h4>Forty-one SNPs in 26 microRNA-related genes were genotyped in 1,097 patients with CRC recruited at the University of Texas MD Anderson Cancer Center (Houston, TX). Patients were enrolled between 1990 and 2008 and last follow-up was in 2010. The a ...[more]

PMID: 22661538

Similar Datasets

Project description:BACKGROUND:Ultraconserved elements (UCEs) are noncoding genomic sequences that completely identical among human, mouse, and rat species and harbor critical biologic functions. The authors hypothesized that single nucleotide polymorphisms (SNPs) within UCEs are associated with clinical outcomes in patients with colorectal cancer (CRC). METHODS:Forty-eight SNPs within UCEs were genotyped in 662 patients with stage I through III CRC. The associations between genotypes and recurrence and survival were analyzed in patients with stage II or III CRC who received fluoropyrimidine-based adjuvant chemotherapy using a training and validation design. The training set included 115 patients with stage II disease and 170 patients with stage III disease, and the validation set included 88 patients with stage II disease and 112 patients with stage III disease. RESULTS:Eight SNPs were associated with clinical outcomes stratified by disease stage. In particular, for patients with stage II CRC who had at least 1 variant allele of reference SNP sequence 7849 (rs7849), a consistent association with increased recurrence risk was observed in the training set (hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.04-5.52), in the replication set (HR, 3.70; 95% CI, 1.42-9.64), and in a meta-analysis (HR, 2.89; 95% CI, 1.54-5.41). Several other SNPs were significant in the training set but not in the validation set. These included rs2421099, rs16983007, and rs10211390 for recurrence and rs6590611 for survival in patients with stage II disease; and SNPs rs6124509 and rs11195893 for recurrence in patients with stage III disease. In addition, a significant cumulative effect was observed of multiple risk genotypes and potential gene-gene interactions on recurrence risk. CONCLUSIONS:To the authors' knowledge, this is the first study to evaluate the association between SNPs within UCEs and clinical outcome in patients with CRC. The results suggested that SNPs within UCEs may be valuable prognostic biomarkers for patients with locally advanced CRC who receive 5-fluorouracil-based chemotherapy.

Project description:PurposeLung cancer tissue includes tumor tissue, stromal cells, immune cells, and epithelial cells. These nontumor cells dilute the tumor purity in lung cancer tissues. Tumor purity plays an essential role in the immune response to lung cancer. At present, the biological processes related to the purity of lung cancer tumors remains unclear.MethodsWe measured tumor purity in 486 lung carcinoma tissues from TCGA-LUAD FPKM by using the "estimate" R package. Lung carcinoma tumor mutation burden was calculated by analyzing TCGA single nucleotide polymorphism data. The immune cell proportion was also evacuated via the CIBERSORT method. Lung carcinoma samples with P < 0.05 were considered significant. Based on the tumor purity and lung carcinoma gene matrix, we performed weighted gene coexpression network analysis (WGCNA), and the tumor purity-related module was identified. Then, we analyzed the functions of the factors involved in the module. We screened the coexpressed factors related to clinical outcome and immunophenotype. Finally, expression levels of these factors were measured at tissue and single-cell levels.ResultsA lung cancer tumor purity correlated coexpression network was determined. Five coexpressed genes (CD4, CD53, EVI2B, PLEK, and SASH3) were identified as tumor purity coexpressed genes that negatively correlated with tumor purity. Because the factors in the coexpression network often participate in similar biological processes, we found that CD4, CD53, EVI2B, PLEK, and SASH3 were most related to positive regulation of cytokine production and interleukin-2 production through functional enrichment. In a clinical phenotype analysis, we found that these five factors can be used as independent prognostic risk factors. We found that these factors were significantly negatively correlated with tumor purity and positively correlated with the immune score in the immunophenotyping analysis. Using GSEA analysis, we found that the antigen processing and presentation pathway were related to the five tumor coexpressed genes mentioned above. SASH3 and CD53 were used to conduct a prognostic model based on the interaction analysis of the Support Vector Machine and the Least Absolute Shrinkage and Selection Operator. SASH3 was verified to be related to CD8A using a single-cell analysis.ConclusionTumor purity-related coexpression factors in the tumor microenvironment have essential clinical, genomic, and biological significance in lung cancer. These coexpression factors (SASH3 and CD53) can be used to classify tumor purity phenotypes and to predict clinical outcomes.

Dataset Information

Genetic polymorphisms in MicroRNA-related genes as predictors of clinical outcomes in colorectal adenocarcinoma patients.

Publications

Genetic polymorphisms in MicroRNA-related genes as predictors of clinical outcomes in colorectal adenocarcinoma patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets