Dataset Information

Comprehensive analysis of histone modification-associated genes on differential gene expression and prognosis in gastric cancer.

ABSTRACT: Accumulating evidence suggests that the epigenetic alterations caused by histone modifications have important roles in the genesis of gastric cancer (GC), particularly the well-studied acetylation and methylation modifications. In the present study, a Bioinformatics analysis of the expression of histone modification-associated genes in GC and normal tissues was performed by using datasets from Oncomine, the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The clinical data of GC patients were downloaded from TCGA to determine the association between histone modification-associated gene expression and clinicopathological parameters or survival of GC. Finally, lysine acetyltransferase 2A (KAT2A), nuclear receptor coactivator 1 (NCOA1), SMYD family member 5 (SMYD5), protein arginine methyltransferase 1 (PRMT1) and PRDF1-RIZ (PR)/Su(var)3-9, enhancer-of-zeste and trithorax (SET) domain 16 (PRDM16) were screened; KAT2A, SMYD5 and PRMT1 were upregulated, while PRDM16 expression was downregulated in GC. Analysis of the GEO and Oncomine datasets revealed that NCOA1 was upregulated, which was contrary to the result obtained with the TCGA stomach adenocarcinoma dataset. Aberrant expression of KAT2A, NCOA1, SMYD5 and PRMT1 was more obvious in gastric intestinal-type adenocarcinoma; low NCOA1 expression was associated with better overall survival of GC patients [hazard ratio (HR)=0.690, 95% CI=0.570-0.840, P<0.001] and was an independent predictor for patients diagnosed with GC (HR=0.639, 95% CI=0.437-0.933, P=0.020). Correlation analysis and protein-protein interaction network analysis indicated a close association between ATAD2 and estrogen receptor 1 (ESR1), PRMT1, NCOA1 and KAT2A. In conclusion, differential expression of KAT2A, NCOA1, SMYD5, PRMT1 and PRDM16 was identified in GC vs. normal tissues, low NCOA1 expression was associated with poor survival of GC and ATAD2 may interact with ESR1 to regulate NCOA1 and PRMT1 in GC.

SUBMITTER: Meng X

PROVIDER: S-EPMC6704541 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Comprehensive analysis of histone modification-associated genes on differential gene expression and prognosis in gastric cancer.

Meng Xiangyu X Zhao Yan Y Liu Jingwei J Wang Lu L Dong Zhe Z Zhang Tao T Gu Xiaohu X Zheng Zhichao Z

Experimental and therapeutic medicine 20190724 3

Accumulating evidence suggests that the epigenetic alterations caused by histone modifications have important roles in the genesis of gastric cancer (GC), particularly the well-studied acetylation and methylation modifications. In the present study, a Bioinformatics analysis of the expression of histone modification-associated genes in GC and normal tissues was performed by using datasets from Oncomine, the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The clinical data of GC ...[more]

PMID: 31452712

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Project description:The solute carrier 30 (SLC30) family genes play a fundamental role in various cancers. However, the diverse expression patterns, prognostic value, and potential mechanism of SLC30A family genes in gastric cancer (GC) remain unknown. Herein, we analyzed the expression and survival data of SLC30A family genes in GC patients using multiple bioinformatic approaches. Expression data of SLC30A family genes for GC patients were extracted from the Cancer Genome Atlas (TCGA) and genetic alteration frequency assessed by using cBioportal database. And validated the expression of SLC30A family genes in GC tissues and corresponding normal tissues. The prognostic value of SLC30A family genes in gastric cancer patients were explored using Kaplan-Meier plotter database. Functional enrichment analysis performed using DAVID database and clusterProfiler package. And ssGSEA algorithm was performed to explore the relationship between the SLC30A family genes and the infiltration of immune cells. We found that the median expression levels of SLC30A1-3, 5-7, and 9 were significantly upregulated in gastric cancer tissues compared to non-cancerous tissues, while SLC30A4 was downregulated. Meanwhile, SLC30A1-7, and 9 were significantly correlated with advanced tumor stage and nodal metastasis status, SLC30A5-7, and 9-10 were significantly related to the Helicobacter pylori infection status of GC patients. High expression of five genes (SLC30A1, 5-7, and 9) was significantly correlated with better overall survival (OS), first progression survival (FPS), and post progression survival (PPS). Conversely, upregulated SLC30A2-4, 8, and 10 expression was markedly associated with poor OS, FP and PPS. And SLC30A family genes were closely associated with the infiltration of immune cells. The present study implied that SLC30A5 and 7 may be potential biomarkers for predicting prognosis in GC patients, SLC30A2 and 3 play an oncogenic role in GC patients and could provide a new strategy for GC patients treatment.

Project description:BackgroundGastric cancer (GC) is one of the most common causes of cancer-related fatalities worldwide, and its progression is associated with RNA modifications. Here, using RNA modification-related genes (RNAMRGs), we aimed to construct a prognostic model for patients with GC.MethodsBased on RNAMRGs, RNA modification scores (RNAMSs) were obtained for GC samples from The Cancer Genome Atlas and were divided into high- and low-RNAMS groups. Differential analysis and weighted correlation network analysis were performed for the differential expressed genes (DEGs) to obtain the key genes. Next, univariate Cox regression, least absolute shrinkage and selection operator, and multivariate Cox regression analyses were performed to obtain the model. According to the model risk score, samples were divided into high- and low-risk groups. Enrichment analysis and immunoassays were performed for the DEGs in these groups. Four external datasets from Gene Expression Omnibus data base were used to test the accuracy of the predictive model.ResultsWe identified SELP and CST2 as key DEGs, which were used to generate the predictive model. The high-risk group had a worse prognosis compared to the low-risk group (p < 0.05). Enrichment analysis and immunoassays revealed that 144 DEGs related to immune cell infiltration were associated with the Wnt signaling pathway and included hub genes such as ELN. Overall mutation levels, tumor mutation burden, and microsatellite instability were lower, but tumor immune dysfunction and exclusion scores were greater (p < 0.05) in the high-risk group than in the low-risk group. The validation results showed that the prediction model score can accurately predict the prognosis of GC patients. Finally, a nomogram was constructed using the risk score combined with the clinicopathological characteristics of patients with GC.ConclusionThis risk score from the prediction model related to the tumor microenvironment and immunotherapy could accurately predict the overall survival of GC patients.

Dataset Information

Comprehensive analysis of histone modification-associated genes on differential gene expression and prognosis in gastric cancer.

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Comprehensive analysis of histone modification-associated genes on differential gene expression and prognosis in gastric cancer.

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