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Non-alcoholic fatty liver disease and colorectal cancer survival.

ABSTRACT: PURPOSE:Liver diseases including non-alcoholic fatty liver disease (NAFLD) and ensuing alterations to the micro-environment may affect development of liver metastasis. Mirroring the rise in obesity rates, prevalence of NAFLD is increasing globally. Our objective was to examine the association between NAFLD and mortality in colorectal cancer patients. METHODS:Colorectal Cancer-Sarcopenia and Near-term Survival (C-SCANS) is a retrospective cohort study which included 3,262 stage I-III patients, aged 18-80 years, and diagnosed between 2006 and 2011 at Kaiser Permanente Northern California. Cox proportional hazards regression was used to calculate multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI). RESULTS:After up to 10 years of follow-up, 879 deaths, including 451 from CRC were identified. Cases diagnosed with NAFLD before and within 1 month after CRC diagnosis (pre-existing NAFLD; n?=?83) had a HR of 1.64 (95% CI 1.06-2.54) for overall and a HR of 1.85 (95% CI 1.03-3.30) for CRC-specific mortality compared to those without NAFLD. Findings did not differ significantly by sex, stage, tumor location, and smoking status, and were also similar when restricted to obese patients only. CONCLUSIONS:Independent of body mass index and prognostic indicators, CRC patients with pre-existing NAFLD had a worse prognosis than those without NAFLD.

SUBMITTER: Wu K

PROVIDER: S-EPMC6613648 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Non-alcoholic fatty liver disease and colorectal cancer survival.

Wu Kana K Zhai Mike Z MZ Weltzien Erin K EK Cespedes Feliciano Elizabeth M EM Meyerhardt Jeffrey A JA Giovannucci Edward E Caan Bette J BJ

Cancer causes & control : CCC 20181115 2

<h4>Purpose</h4>Liver diseases including non-alcoholic fatty liver disease (NAFLD) and ensuing alterations to the micro-environment may affect development of liver metastasis. Mirroring the rise in obesity rates, prevalence of NAFLD is increasing globally. Our objective was to examine the association between NAFLD and mortality in colorectal cancer patients.<h4>Methods</h4>Colorectal Cancer-Sarcopenia and Near-term Survival (C-SCANS) is a retrospective cohort study which included 3,262 stage I-I ...[more]

PMID: 30443695

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Project description:Background: Given the ongoing research on non-alcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC), the number of studies suggesting a strong link between NAFLD and CRC is on the rise, while its underlying pathological mechanisms remain uncertain. This study aims to explore the shared genes and mechanisms and to reveal the molecular basis of the association between CRC and NAFLD through bioinformatics approaches. Methods: The Gene Expression Omnibus (GEO) dataset GSE89632 is downloaded for NAFLD cases and healthy controls. Additionally, the GSE4107 and GSE9348 datasets are obtained for CRC cases and healthy controls. Differentially expressed genes (DEGs) are obtained for NAFLD and CRC datasets, as well as shared genes between the two disorders. GO and KEGG enrichment analyses are further conducted. Subsequently, the STRING database and Cytoscape software are utilized to establish the PPI network and identify the hub genes. Then, co-expression analysis is performed using GeneMANIA. Subsequently, ROC curves and external datasets validation were applied to further screen the candidate markers. Finally, NetworkAnalyst is available as a means to construct a miRNA-gene regulatory network. Results: Under the threshold of FDR ≤ 0.01, 147 common genes are obtained in NAFLD and CRC. Categorization of GO functions shows that DEGs are predominantly enriched in "response to organic substance", "cellular response to chemical stimulus", and "response to external stimulus". The predominant KEGG pathways in DEGs are the "IL-17 signaling pathway", the "TNF signaling pathway", "Viral protein interaction with cytokine and cytokine receptor", "Cytokine-cytokine receptor interaction", and the "Toll-like receptor signaling pathway". Additionally, MYC, IL1B, FOS, CXCL8, PTGS2, MMP9, JUN, and IL6 are identified as hub genes by the evaluation of 7 algorithms. With the construction of miRNA-gene networks, 2 miRNAs, including miR-106a-5p, and miR-204-5p are predicted to be potential key miRNAs. Conclusion: This study identifies possible hub genes acting in the co-morbidity of NAFLD and CRC and discovers the interaction of miRNAs and hub genes, providing a novel understanding of the molecular basis for the relevance of CRC and NAFLD, thus contributing to the development of new therapeutic strategies to combat NAFLD and CRC.

Dataset Information

Non-alcoholic fatty liver disease and colorectal cancer survival.

Publications

Non-alcoholic fatty liver disease and colorectal cancer survival.

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