Dataset Information

Hypermethylation of N-Acetyltransferase 1 Is a Prognostic Biomarker in Colon Adenocarcinoma.

ABSTRACT: Background: The N-acetyltransferase 1 (NAT1) gene is downregulated in several cancers and associated with patient survival. In this study, we sought to examine the prognostic value and clinical significance of NAT1 methylation in colon adenocarcinoma (COAD). Methods: Data relating to NAT1 mRNA expression and methylation and clinicopathological features of COAD were extracted from the database of The Cancer Genome Atlas. We compared the mRNA expression and methylation of NAT1 between COAD and normal tissues and performed correlation analysis to assess the association between NAT1 mRNA expression and methylation. Furthermore, we assessed patient survival based on CpG sites in the promoter region of NAT1 and analyzed the association between the NAT1 mRNA expression and CpG site methylation and clinicopathological features. An independent Gene Expression Omnibus (GEO) dataset was used to validate the results. Results: We found that the expression of NAT1 mRNA was reduced in COAD compared with normal tissues and that mean methylation of the eight CpG sites in the promoter region of NAT1 was higher in COAD tissues than in normal tissues. Furthermore, five CpG sites were demonstrated to be significantly negatively correlated with NAT1 mRNA expression in COAD. Survival analysis indicated that NAT1 mRNA expression and the cg15797286 and cg18509990 sites were associated with the overall survival of COAD patients. Combined survival analysis revealed that combinations of NAT1 mRNA expression with five CpG sites were significantly associated with the overall survival of COAD patients. Both NAT1 mRNA and cg15797286 were associated with the T, N, and clinical stages of COAD. The GEO data indicated that cg15797286 was hypermethylated in recurrent colorectal adenomas. Conclusions: Methylation of NAT1 is associated with the development of COAD, and may serve as prognostic and treatment biomarkers for COAD.

SUBMITTER: Shi C

PROVIDER: S-EPMC6851262 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Hypermethylation of N-Acetyltransferase 1 Is a Prognostic Biomarker in Colon Adenocarcinoma.

Shi Cheng C Xie Li-Ye LY Tang Yan-Ping YP Long Long L Li Ji-Lin JL Hu Bang-Li BL Li Ke-Zhi KZ

Frontiers in genetics 20191106

Background: The N-acetyltransferase 1 (NAT1) gene is downregulated in several cancers and associated with patient survival. In this study, we sought to examine the prognostic value and clinical significance of NAT1 methylation in colon adenocarcinoma (COAD). Methods: Data relating to NAT1 mRNA expression and methylation and clinicopathological features of COAD were extracted from the database of The Cancer Genome Atlas. We compared the mRNA expression an ...[more]

PMID: 31781164

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Project description:Colon adenocarcinoma (COAD) is one of the most serious cancers. It is important to accurately predict prognosis and provide individualized treatment. Evidence suggests that clinicopathological features and immune status of the body are related to the occurrence and development of cancer. Expression of long non-coding RNA (LncRNA) ALMS1 intronic transcript 1 (ALMS1-IT1) is observed in some cancer types, and we believe that it may have the potential to serve as a marker of COAD. Therefore, we used the data obtained from the cancer genome atlas (TCGA) database to prove the relationship between ALMS1-IT1 and COAD. Wilcoxon rank sum test, Chi-square test, Fisher exact test and logistic regression were used to evaluate relationships between clinical-pathologic features and ALMS1-IT1 expression. Receiver operating characteristic curves were used to describe binary classifier value of ALMS1-IT1 using area under curve score. Kaplan-Meier method and Cox regression analysis were used to evaluate factors contributing to prognosis. Gene oncology (GO) and (Kyoto Encyclopedia of Genes and Genomes) KEGG enrichment analysis were used to predict the function of differentially expressed genes associated with ALMS1-IT1. Gene set enrichment analysis (GSEA) was used to predict canonical pathways associated with ALMS1-IT1.Immune infiltration analysis was performed to identify the significantly involved functions of ALMS1-IT1. Starbase database was used to predict miRNAs and RNA binding proteins (RBPs) that may interact with ALMS1-IT1. Increased ALMS1-IT1 expression in COAD was associated with N stage (P < .001), M stage (P = .003), Pathologic stage (P = .002), and Primary therapy outcome (P = .009). Receiver operating characteristic curve suggested the significant diagnostic and prognostic ability of ALMS1-IT1 (area under curve = 0.857). High ALMS1-IT1 expression predicted a poorer overall-survival (P = .005) and poorer progression-free interval (PFI) (P = .012), and ALMS1-IT1 expression was independently correlated with PFI in COAD patients (hazard ratio (HR) :1.468; 95% CI: 1.029-2.093; P =.034) (HR: 1.468; 95% CI: 1.029-2.093; P = .034). GO, KEGG, GSEA, and immune infiltration analysis showed that ALMS1-IT1 expression was correlated with regulating the function of DNA and some types of immune infiltrating cells. ALMS1-IT1 expression was significantly correlated with poor survival and immune infiltrations in COAD, and it may be a promising prognostic biomarker in COAD.

Project description:The aim of the present study was to examine the molecular factors associated with the prognosis of colon cancer. Gene expression datasets were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases to screen differentially expressed genes (DEGs) between colon cancer samples and normal samples. Survival?related genes were selected from the DEGs using the Cox regression method. A co?expression network of survival?related genes was then constructed, and functional clusters were extracted from this network. The significantly enriched functions and pathways of the genes in the network were identified. Using Bayesian discriminant analysis, a prognostic prediction system was established to distinguish the positive from negative prognostic samples. The discrimination efficacy of the system was validated in the GSE17538 dataset using Kaplan?Meier survival analysis. A total of 636 and 1,892 DEGs between the colon cancer samples and normal samples were screened from the TCGA and GSE44861 dataset, respectively. There were 155 survival?related genes selected. The co?expression network of survival?related genes included 138 genes, 534 lines (connections) and five functional clusters, including the signaling pathway, cellular response to cAMP, and immune system process functional clusters. The molecular function, cellular components and biological processes were the significantly enriched functions. The peroxisome proliferator?activated receptor signaling pathway, Wnt signaling pathway, B cell receptor signaling pathway, and cytokine?cytokine receptor interactions were the significant pathways. A prognostic prediction system based on a 65?gene signature was established using this co?expression network. Its discriminatory effect was validated in the TCGA dataset (P=3.56e?12) and the GSE17538 dataset (P=1.67e?6). The 65?gene signature included kallikrein?related peptidase 6 (KLK6), collagen type XI ?1 (COL11A1), cartilage oligomeric matrix protein, wingless?type MMTV integration site family member 2 (WNT2) and keratin 6B. In conclusion, a 65?gene signature was screened in the present study, which showed a prognostic prediction effect in colon adenocarcinoma. KLK6, COL11A1, and WNT2 may be suitable prognostic predictors for colon adenocarcinoma.

Dataset Information

Hypermethylation of N-Acetyltransferase 1 Is a Prognostic Biomarker in Colon Adenocarcinoma.

Publications

Hypermethylation of <i>N</i>-Acetyltransferase 1 Is a Prognostic Biomarker in Colon Adenocarcinoma.

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