Dataset Information

Tumor-preventing activity of aspirin in multiple cancers based on bioinformatic analyses.

ABSTRACT:

Background

Acetylsalicylic acid was renamed aspirin in 1899, and it has been widely used for its multiple biological actions. Because of the diversity of the cellular processes and diseases that aspirin reportedly affects and benefits, uncertainty remains regarding its mechanism in different biological systems.

Methods

The Drugbank and STITCH databases were used to find direct protein targets (DPTs) of aspirin. The Mentha database was used to analyze protein-protein interactions (PPIs) to find DPT-associated genes. DAVID was used for the GO and KEGG enrichment analyses. The cBio Cancer Genomics Portal database was used to mine genetic alterations and networks of aspirin-associated genes in cancer.

Results

Eighteen direct protein targets (DPT) and 961 DPT-associated genes were identified for aspirin. This enrichment analysis resulted in eight identified KEGG pathways that were associated with cancers. Analysis using the cBio portal indicated that aspirin might have effects on multiple tumor suppressors, such as TP53, PTEN, and RB1 and that TP53 might play a central role in aspirin-associated genes.

Discussion

The results not only suggest that aspirin might have anti-tumor actions against multiple cancers but could also provide new directions for further research on aspirin using a bioinformatics analysis approach.

SUBMITTER: Li D

PROVIDER: S-EPMC6163034 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Tumor-preventing activity of aspirin in multiple cancers based on bioinformatic analyses.

Li Diangeng D Wang Peng P Yu Yi Y Huang Bing B Zhang Xuelin X Xu Chou C Zhao Xian X Yin Zhiwei Z He Zheng Z Jin Meiling M Liu Changting C

PeerJ 20180926

<h4>Background</h4>Acetylsalicylic acid was renamed aspirin in 1899, and it has been widely used for its multiple biological actions. Because of the diversity of the cellular processes and diseases that aspirin reportedly affects and benefits, uncertainty remains regarding its mechanism in different biological systems.<h4>Methods</h4>The Drugbank and STITCH databases were used to find direct protein targets (DPTs) of aspirin. The Mentha database was used to analyze protein-protein interactions ( ...[more]

PMID: 30280037

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Project description:Background & aimsAspirin use reduces colorectal cancer risk. Aspirin, a nonsteroidal anti-inflammatory drug, inhibits prostaglandin-endoperoxide synthase 2 (PTGS2 or cyclooxygenase-2); PTGS2 promotes inflammation and suppresses T-cell-mediated adaptive immunity. We investigated whether the inverse association of aspirin use with colorectal carcinoma risk was stronger for tumors with lower degrees of lymphocytic infiltrates than for tumors with higher degrees of lymphocytic infiltrates.MethodsWe collected aspirin use data biennially from participants in the Nurses' Health Study and Health Professionals Follow-up Study. Participants were asked whether they took aspirin in most weeks, the number of tablets taken per week, and years of aspirin use. We collected available tumor specimens (n = 1458) from pathology laboratories in the United States. A pathologist confirmed the diagnosis of colorectal adenocarcinoma (excluding anal squamous cell carcinoma), and evaluated histopathology features, including patterns and degrees of lymphocytic infiltrates within and around tumor areas. Person-years of follow-up evaluation were accrued from the date of return of questionnaires until dates of colorectal cancer diagnosis, death, or the end of follow-up evaluation (June 2010). Duplication-method Cox proportional hazards regression was used to assess the association of aspirin with the incidence of colorectal carcinoma subgroups according to the degree of tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral reaction, or Crohn's-like reaction.ResultsWe documented 1458 rectal and colon cancers. The inverse association between regular aspirin use and colorectal cancer risk significantly differed by concentrations of TILs (Pheterogeneity = .007). Compared with nonregular use, regular aspirin use was associated with a lower risk of tumors that had low levels of TILs (relative risk, 0.72; 95% confidence interval, 0.63-0.81), and strength of the association depended on aspirin dose and duration (both Ptrend < .001). In contrast, aspirin use was not associated with a risk of tumors having intermediate or high levels of TILs. This differential association was consistent regardless of the status of tumor microsatellite instability, mutations in BRAF, or expression of PTGS2. Regular aspirin use was associated with a lower risk of tumors that contained low levels of CD3+ T cells, CD8+ T cells, or CD45RO (PTPRC)+ T cells (measured by immunohistochemistry and computer-assisted image analysis).ConclusionsBased on data from the prospective cohort studies, regular use of aspirin is associated with a lower risk of colorectal carcinomas with low concentrations of TILs. These findings indicate that the immune response in the tumor microenvironment could be involved in the chemopreventive effects of aspirin.

Project description:ObjectiveTo explore the molecular mechanism underlying the inhibitory effects of aspirin against human breast cancer cell proliferation through bioinformatics analysis.MethodsDrug Bank 5.1.3 was searched to identify direct protein targets (DPTs) of aspirin, and the protein-protein interaction (PPI) network of the DPTs was constructed online using STRING and the signaling pathways involved were identified. The genetic alterations of 6 DPTs associated with human breast cancer was analyzed and visualized by cBio Portal and OncoPrint, respectively. The transcriptomic data of breast cancer and normal tissues were downloaded from TCGA database, and the overexpressed genes were analyzed by DECenter. The intersection between the genes associated with the DPTs obtained by STRING analysis and the differentially over-expressed genes in TCGA was determined to confirm the candidate DPTs as a potential target of aspirin, and GO functional enrichment analysis was performed using Gene Ontology. The potential targets of aspirin against the proliferation of human breast cancer cells were verified by Western blotting.ResultsEleven DPTs of aspirin were identified. KEGG pathway enrichment indicated that 6 genes (EDNRA, IKBKB, NFKB2, NFKBIA, PTGS2 and TP53) were associated with the occurrence and development of cancer. A total of 10 220 differentially expressed genes were identified from the TCGA database, and among them 4 genes (CDC25C, TPX2, CDC20, PLK1) were found to be the potential targets for aspirin. These genes were involved mostly in the regulation of cell cycle and cell division. Western blotting showed that aspirin could down-regulate the expression levels of several pivotal proteins that regulated cell cycle and cell division, including CDC25C, TPX2, CDC20 and PLK1.ConclusionsCDC25C, TPX2, CDC20 and PLK1 may be potential targets for aspirin to inhibit the proliferation of human breast cancer cells, by affecting the progress of cell cycle and cell division.

Dataset Information

Tumor-preventing activity of aspirin in multiple cancers based on bioinformatic analyses.

Background

Methods

Results

Discussion

Publications

Tumor-preventing activity of aspirin in multiple cancers based on bioinformatic analyses.

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