Dataset Information

Expression analysis of apolipoprotein E and its associated genes in gastric cancer.

ABSTRACT: Gastric cancer is a common type of cancer worldwide, and has a poor prognosis, in part due to the low rates of early diagnosis and the limited treatment methods available. Apolipoprotein E (ApoE) is involved in exogenous cholesterol transport and may be important in enabling tumor cells to fulfill their high cholesterol requirements. A number of reports have indicated that ApoE affects the development and prognosis of gastric cancer. Therefore, the aim of the present study was to investigate the genes and transcription factors that interact with ApoE during the development of gastric cancer. Using gene expression profiling, the BioGRID database and the transcriptional regulatory element database, gene expression and regulatory networks in gastric cancer tissues and adjacent normal tissues were analyzed. The data demonstrated that eight genes associated with ApoE were differentially expressed, with six of these upregulated and two downregulated. Functionally, these genes were involved in the JAK-STAT cascade, acute-phase response, acute inflammatory response, and the steroid hormone response. Among these ApoE-associated genes, expression of the signal transducer and activator of transcription 2 (STAT2) and STAT3 transcription factors was upregulated. To the best of our knowledge, this is the first study to demonstrate the network of ApoE-related genes and transcription factors in gastric cancer. Additional studies are required in order to confirm these data and to translate the results into the identification of clinical biomarkers and novel treatment strategies for gastric cancer.

SUBMITTER: Shi X

PROVIDER: S-EPMC4533697 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Expression analysis of apolipoprotein E and its associated genes in gastric cancer.

Shi Xiumin X Xu Jianting J Wang Jihan J Cui Meizi M Gao Yushun Y Niu Haitao H Jin Haofan H

Oncology letters 20150701 3

Gastric cancer is a common type of cancer worldwide, and has a poor prognosis, in part due to the low rates of early diagnosis and the limited treatment methods available. Apolipoprotein E (ApoE) is involved in exogenous cholesterol transport and may be important in enabling tumor cells to fulfill their high cholesterol requirements. A number of reports have indicated that ApoE affects the development and prognosis of gastric cancer. Therefore, the aim of the present study was to investigate the ...[more]

PMID: 26622669

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Project description:Purpose: Gastric cancer (GC) is a primary cause of cancer-associated mortality worldwide. N6-methyladenosine (m6A) is one of the most common RNA modifications that involves in the progression of numerous cancers. However, the expression status and function of m6A-related genes in gastric cancer is still not well understood. The current study is aimed to investigate the expression status and determinate prognostic value of m6A-related genes in gastric cancer. Methods: m6A-asssociated gene expression was evaluated via analyzing the expression data of GC patients from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The protein expression levels of m6A-associated molecules were further validated by immunohistochemical (IHC) staining data from GC tissue microarray (TMA) cohort and Human Protein Atlas (HPA) database. Kaplan-Meier analysis was performed to assess the prognostic value of m6A-associated genes in gastric cancer. Risk score model was established by lasso COX regression analysis and its prognostic predicted efficiency was assessed by the receiver-operator characteristic (ROC) curve. Cox regression analyses were used for exploring risk factors related to GC patient prognosis. Results: Most of m6A-related genes were upregulated at both mRNA and protein levels in gastric cancer tissues compared with that in normal gastric tissues. The expression levels of m6A-related genes were associated with clinicopathological features including race, age and TNM stage. High expression of WTAP and FTO predicted poor prognosis of GC patients. Survival analysis demonstrated that patients with high-risk scores had worse overall survival (OS) and ROC curves suggested the prediction performance for gastric patients. Moreover, Cox regression analyses indicated that m6A risk model score was a prognostic factor for OS and FTO upregulation might be a potential independent prognostic factor for recurrence-free survival (RFS) in gastric cancer patients. Conclusion: m6A-related genes were dysregulated in GC and were closely associated with prognosis of GC patients. FTO might serve as a novel prognostic biomarker for gastric cancer, while the m6A-related risk score might be informative for risk assessment and prognostic stratification.

Project description:PurposeThe current treatment methods available for advanced gastric cancer are not very promising. Hence, it is important to explore novel biomarkers and potential therapeutic agents to treat gastric cancer (GC). This study aimed to identify hub genes associated with GC prognosis and explore potential drugs for its treatment.Materials and methodsThree gene expression data of GC and normal tissues were downloaded from the Gene Expression Omnibus (GEO) and processed to identify the differentially expressed genes (DEGs). We conducted a comprehensive analysis of DEGs, including functional enrichment analysis, construction of protein-protein interaction (PPI) network, identification of hub genes, survival analysis and expression verification of hub genes. Finally, we constructed the network of miRNA-mRNA, and predicted the drugs that might be effective for GC treatment.ResultsA total of 340 DEGs, including 94 up-regulated and 246 down-regulated genes, were identified. Among the up-regulated DEGs, the enrichment terms were primarily related to tumorigenesis and tumor progression, extracellular matrix organization, and collagen catabolic process. Additionally, 10 hub genes (FN1, COL3A1, COL1A2, BGN, THBS2, COL5A2, THBS1, COL5A1, SPARC, and COL4A1) were identified, out of which 7 genes were significantly associated with poor overall survival (OS) in GC. The expression levels of these 7 hub genes were verified using real-time PCR, immunohistochemistry, and the GEPIA2 (Gene Expression Profiling Interactive Analysis) server. A regulatory network of miRNA-mRNA was also constructed, and the top 4 interactive miRNAs (hsa-miR-29b-3p, hsa-miR-140-3p, hsa-miR-29a-3p, and hsa-miR-29c-3p) that targeted the most hub genes were identified. Finally, fourteen small molecules were predicted to be effective in treating GC.ConclusionThe identification of the hub genes, miRNA-mRNA network, and potential candidate drugs associated with GC provides new insights into the molecular mechanisms and treatment of GC.

Project description:BackgroundGastric cancer (GC) is one of the common gastrointestinal malignancy worldwide and exhibits a poor prognosis. Increasing studies have indicated that microRNAs play critical roles in the cancer progression and have shown great potential as useful biomarkers. The search for potential diagnostic and prognostic biomarkers of gastric cancer (GC) with integrated bioinformatics analyses has been undertaken in previous studies.MethodsIn this study, the robust rank aggregation (RRA) method was used to perform an integrated analysis of differentially expressed miRNAs (DEMs) from five microarray datasets in the Gene Expression Omnibus (GEO) database to find robust biomarkers for GC. Ultimately, seven miRNAs were filtered from fourteen primary miRNAs using the validation set of The Cancer Genome Atlas (TCGA) database. Based on these results, diagnostic and survival analyses were performed, and logistic regression and Cox regression were used to determine the clinicopathological characteristics of the DEM expression and overall survival.ResultsNine eligible miRNA datasets related to GC were selected from the GEO database for integrated analysis in this study. Diagnostic analysis implied that these miRNAs could be regarded as promising candidate diagnostic biomarkers in GC tissues, but whether the results of the tissue analysis are consistent with those of peripheral blood analysis requires further validation. The logistic regression indicated that the ectopic expression of these DEMs was relevant to the histological type, anatomical region, and pathological grade of GC. However, the survival and Cox regression analyses suggested that the poor prognosis of GC patients was not strongly dependent on the ectopic expression of the seven miRNAs, but rather, a poor prognosis was associated with age, metastasis, and histological grade.ConclusionsBased on the results presented in this study it can be concluded that these miRNAs (miR-455-3p, miR-135b-5p, let-7a-3p, miR-195-5p, miR-204-5p, miR-149-5p, and miR-143-3p) might be potential biomarkers for the early diagnosis of GC patients, but this finding should be regarded with caution. A large-scale, prospective, and multicenter cohort study should be performed.

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Expression analysis of apolipoprotein E and its associated genes in gastric cancer.

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Expression analysis of apolipoprotein E and its associated genes in gastric cancer.

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