Molecular Mechanism of Aflatoxin-Induced Hepatocellular Carcinoma Derived from a Bioinformatics Analysis

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Abstract

Exposure to aflatoxin is considered to be one of the causes of hepatocellular carcinoma (HCC). With the development of bioinformation, we sought to reveal the occurrence and development of aflatoxin-induced HCC through data research. We identified differentially expressed genes (DEGs) of datasets GSE127791 (Aflatoxin-treated pluripotent stem cell derived human hepatocytes vs. controls) and GSE64041 (liver carcinoma with unknown cause vs. non-cancerous tissue) by GEO2R to find the common DEGs. Gene ontology (GO) and KEGG path enrichment analysis were used to annotate the function of DEGs. Hub genes were screened from identified DEGs by protein-protein interaction (PPI) network analysis. The prognostic value of hub genes in cancer databases were evaluated. We obtained 132 common DEGs and 11 hub genes. According to cluster analysis and protein co-expression networks, we screened out the key genes, histidine-rich glycoprotein (HRG) and phosphoenolpyruvate carboxykinase 2 (PCK2). Oncomine database and survival curve analysis showed that the decline in HRG and PCK2 expression in the development of HCC indicated poor prognosis. We speculated that the decreased expression of HRG and PCK2 after aflatoxin exposure to hepatocyte may be related to aflatoxin induced hepatocyte injury and carcinogenesis. In addition, the decreased expression of HRG and PCK2 in the occurrence and development of HCC suggests a poor prognosis of HCC.

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Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

J. Gao, B. A. Aksoy, U Dogrusoz … (2015)

The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.

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HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF.

Charlotte Rolny, Massimiliano Mazzone, Sònia Tugues … (2011)

Polarization of tumor-associated macrophages (TAMs) to a proangiogenic/immune-suppressive (M2-like) phenotype and abnormal, hypoperfused vessels are hallmarks of malignancy, but their molecular basis and interrelationship remains enigmatic. We report that the host-produced histidine-rich glycoprotein (HRG) inhibits tumor growth and metastasis, while improving chemotherapy. By skewing TAM polarization away from the M2- to a tumor-inhibiting M1-like phenotype, HRG promotes antitumor immune responses and vessel normalization, effects known to decrease tumor growth and metastasis and to enhance chemotherapy. Skewing of TAM polarization by HRG relies substantially on downregulation of placental growth factor (PlGF). Besides unveiling an important role for TAM polarization in tumor vessel abnormalization, and its regulation by HRG/PlGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment. Copyright Â© 2011 Elsevier Inc. All rights reserved.

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Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma

Otília Menyhart, Adam J. Nagy, Balázs Győrffy (2018)

Background: Potential prognostic biomarker candidates for hepatocellular carcinoma (HCC) are abundant, but their generalizability is unexplored. We cross-validated markers of overall survival (OS) and vascular invasion in independent datasets. Methods: The literature search yielded 318 genes related to survival and 52 related to vascular invasion. Validation was performed in three datasets (RNA-seq, n = 371; Affymetrix arrays, n = 91; Illumina gene chips, n = 135) by uni- and multivariate Cox regression and Mann–Whitney U-test, separately for Asian and Caucasian patients. Results: One hundred and eighty biomarkers remained significant in Asian and 128 in Caucasian subjects at p < 0.05. After multiple testing correction BIRC5 (p = 1.9 × 10−10), CDC20 (p = 2.5 × 10−9) and PLK1 (p = 3 × 10−9) endured as best performing genes in Asian patients; however, none remained significant in the Caucasian cohort. In a multivariate analysis, significance was reached by stage (p = 0.0018) and expression of CENPH (p = 0.0038) and CDK4 (p = 0.038). KIF18A was the only gene predicting vascular invasion in the Affymetrix and Illumina cohorts (p = 0.003 and p = 0.025, respectively). Conclusion: Overall, about half of biomarker candidates failed to retain prognostic value and none were better than stage predicting OS. Impact: Our results help to eliminate biomarkers with limited capability to predict OS and/or vascular invasion.

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Journal

Journal ID (nlm-ta): Toxins (Basel)

Journal ID (iso-abbrev): Toxins (Basel)

Journal ID (publisher-id): toxins

Title: Toxins

Publisher: MDPI

ISSN (Electronic): 2072-6651

Publication date (Electronic): 23 March 2020

Publication date Collection: March 2020

Volume: 12

Issue: 3

Electronic Location Identifier: 203

Affiliations

[1 ]College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; MX120170756@ 123456yzu.edu.cn (P.C.); yuanyan@ 123456yzu.edu.cn (Y.Y.);

[2 ]Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China

[3 ]Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China

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[* ]Correspondence: jcbian@ 123456yzu.edu.cn ; Tel.: +86-514-87979042

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Jianchun Bian https://orcid.org/0000-0001-8023-0751

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Publisher ID: toxins-12-00203

DOI: 10.3390/toxins12030203

PMC ID: 7150856

PubMed ID: 32210020

SO-VID: 156cdf1e-1f95-45ee-a0cd-f7997c4e369c

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Molecular Mechanism of Aflatoxin-Induced Hepatocellular Carcinoma Derived from a Bioinformatics Analysis

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Most cited references 34

Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal.

HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF.

Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma

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