Bioinformatic analysis reveals CYP2C9 as a potential prognostic marker for HCC and liver cancer cell lines suitable for its mechanism study

Liu Shuaichen; Wang Guangyi

doi:10.14715/cmb/2018.64.7.12

Issue

Vol. 64 No. 7: Issue 7

Issue Published : June 12, 2018

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Bioinformatic analysis reveals CYP2C9 as a potential prognostic marker for HCC and liver cancer cell lines suitable for its mechanism study

https://doi.org/10.14715/cmb/2018.64.7.12

Liu Shuaichen

Department of Hepatobiliary & Pancreas Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021, China

Wang Guangyi

Department of Hepatobiliary & Pancreas Surgery, The First Hospital, Jilin University, Changchun, Jilin 130021, China

Corresponding Author(s) : Wang Guangyi

rz1332@163.com

Cellular and Molecular Biology, Vol. 64 No. 7: Issue 7
Article Published : May 30, 2018

Abstract

Hepatocellular carcinoma (HCC) is a common cancer and the sixth most lethal malignancy in the world. We chose gene expression profile of GSE14520 from GEO database aiming to find key genes that affect HCC progression. 22 paired tumor and non-tumor samples were included in this analysis. Differentially expressed genes (DEGs) between tumor and non-tumor were selected using GEO2R. Gene ontology (GO) enrichment and protein-protein interaction (PPI) of the DEGs were done using Metascape. There were 357 DEGs, including 70 up-regulated genes and 287 down-regulated genes. These DEGs were enriched in drug metabolic process, organic acid catabolic process, monocarboxylic metabolic process and etc. Three important modules were detected from PPI network using Molecular Complex Detection (MCODE) algorithm. Moreover, the Kaplan–Meier analysis for overall survival and disease-free survival were applied to those genes in top PPI group. In conclusion, this bioinformatic analysis demonstrated that DEGs, such as CYP2C9, might promote the development of HCC, especially in drug metabolism. It could also be used as a new biomarker for diagnosis.

Keywords

HCC CYPs Prognosis Metascape Differentially expressed genes.

Shuaichen, L., & Guangyi, W. (2018). Bioinformatic analysis reveals CYP2C9 as a potential prognostic marker for HCC and liver cancer cell lines suitable for its mechanism study. Cellular and Molecular Biology, 64(7), 70–74. https://doi.org/10.14715/cmb/2018.64.7.12

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References

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Parkin DM, The global health burden of infection-associated cancers in the year 2002. International journal of cancer 2006, 118, 3030-3044.
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Guengerich FP. Cytochrome p450 and chemical toxicology. Chemical research in toxicology 2008, 21, 70-83.
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Tripathi S, Pohl MO, Zhou Y, Rodriguez-Frandsen A, Wang G, Stein DA et al. Meta- and orthogonal integration of influenza "omics" data defines a role for ubr4 in virus budding. Cell host & microbe 2015, 18, 723-735.
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Interactive human protein atlas launches. Cancer discovery 2015, 5, 339.
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Goldstein JA, de Morais SM. Biochemistry and molecular biology of the human cyp2c subfamily. Pharmacogenetics 1994, 4, 285-299.
Miners JO, Birkett DJ. Cytochrome p4502c9: An enzyme of major importance in human drug metabolism. British journal of clinical pharmacology 1998, 45, 525-538.
Chen H, Shen ZY, Xu W, Fan TY, Li J, Lu YF et al. Expression of p450 and nuclear receptors in normal and end-stage chinese livers. World journal of gastroenterology 2014, 20, 8681-8690.
Ye L, Yang X, Guo E, Chen W, Lu L, Wang Y et al. Sorafenib metabolism is significantly altered in the liver tumor tissue of hepatocellular carcinoma patient. PloS one 2014, 9, e96664.
Pentikainen PJ, Valisalmi L, Himberg JJ, Crevoisier C. Pharmacokinetics of midazolam following intravenous and oral administration in patients with chronic liver disease and in healthy subjects. Journal of clinical pharmacology 1989, 29, 272-277.
MacGilchrist AJ, Birnie GG, Cook A, Scobie G, Murray T, Watkinson G et al. Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis. Gut 1986, 27, 190-195.
Andersson T, Olsson R, Regardh CG, Skanberg I. Pharmacokinetics of [14c] omeprazole in patients with liver cirrhosis. Clinical pharmacokinetics 1993, 24, 71-78.
Gao J, Zhou J, He XP, Zhang YF, Gao N, Tian X et al. Changes in cytochrome p450s-mediated drug clearance in patients with hepatocellular carcinoma in vitro and in vivo: A bottom-up approach. Oncotarget 2016, 7, 28612-28623.
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Yin L, Chang C, Xu C. G2/m checkpoint plays a vital role at the early stage of hcc by analysis of key pathways and genes. Oncotarget 2017, 8, 76305-76317.
Yan T, Lu L, Xie C, Chen J, Peng X, Zhu L et al. Severely impaired and dysregulated cytochrome p450 expression and activities in hepatocellular carcinoma: Implications for personalized treatment in patients. Molecular cancer therapeutics 2015, 14, 2874-2886.

References

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012.CA: a cancer journal for clinicians 2015, 65, 87-108.

Parkin DM, The global health burden of infection-associated cancers in the year 2002. International journal of cancer 2006, 118, 3030-3044.

Tang A, Hallouch O, Chernyak V, Kamaya A, Sirlin CB. Epidemiology of hepatocellular carcinoma: Target population for surveillance and diagnosis. Abdominal radiology (New York) 2018, 43, 13-25.

Yu D, Green B, Marrone A, Guo Y, Kadlubar S, Lin D et al. Suppression of cyp2c9 by microrna hsa-mir-128-3p in human liver cells and association with hepatocellular carcinoma. Scientific reports 2015, 5, 8534.

Korobkova EA. Effect of natural polyphenols on cyp metabolism: Implications for diseases. Chemical research in toxicology 2015, 28, 1359-1390.

Guengerich FP. Cytochrome p450 and chemical toxicology. Chemical research in toxicology 2008, 21, 70-83.

Nebert DW, Dalton TP. The role of cytochrome p450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nature reviews. Cancer 2006, 6, 947-960.

Zhao X, Chen Y, Mao Q, Jiang X, Jiang W, Chen J et al. Overexpression of ythdf1 is associated with poor prognosis in patients with hepatocellular carcinoma. Cancer biomarkers: section A of Disease markers 2018, 21, 859-868.

Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S et al. The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 2012, 483, 603-607.

Davis S, Meltzer PS. Geoquery: A bridge between the gene expression omnibus (geo) and bioconductor. Bioinformatics (Oxford, England) 2007, 23, 1846-1847.

Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM et al. Gene ontology: Tool for the unification of biology. The gene ontology consortium. Nature genetics 2000, 25, 25-29.

Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M. Kegg: Kyoto encyclopedia of genes and genomes. Nucleic acids research 1999, 27, 29-34.

Tripathi S, Pohl MO, Zhou Y, Rodriguez-Frandsen A, Wang G, Stein DA et al. Meta- and orthogonal integration of influenza "omics" data defines a role for ubr4 in virus budding. Cell host & microbe 2015, 18, 723-735.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. Gepia: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic acids research 2017, 45, W98-w102.

Interactive human protein atlas launches. Cancer discovery 2015, 5, 339.

Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A et al. Proteomics. Tissue-based map of the human proteome. Science (New York, N.Y.) 2015, 347, 1260419.

Goldstein JA, de Morais SM. Biochemistry and molecular biology of the human cyp2c subfamily. Pharmacogenetics 1994, 4, 285-299.

Miners JO, Birkett DJ. Cytochrome p4502c9: An enzyme of major importance in human drug metabolism. British journal of clinical pharmacology 1998, 45, 525-538.

Chen H, Shen ZY, Xu W, Fan TY, Li J, Lu YF et al. Expression of p450 and nuclear receptors in normal and end-stage chinese livers. World journal of gastroenterology 2014, 20, 8681-8690.

Ye L, Yang X, Guo E, Chen W, Lu L, Wang Y et al. Sorafenib metabolism is significantly altered in the liver tumor tissue of hepatocellular carcinoma patient. PloS one 2014, 9, e96664.

Pentikainen PJ, Valisalmi L, Himberg JJ, Crevoisier C. Pharmacokinetics of midazolam following intravenous and oral administration in patients with chronic liver disease and in healthy subjects. Journal of clinical pharmacology 1989, 29, 272-277.

MacGilchrist AJ, Birnie GG, Cook A, Scobie G, Murray T, Watkinson G et al. Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis. Gut 1986, 27, 190-195.

Andersson T, Olsson R, Regardh CG, Skanberg I. Pharmacokinetics of [14c] omeprazole in patients with liver cirrhosis. Clinical pharmacokinetics 1993, 24, 71-78.

Gao J, Zhou J, He XP, Zhang YF, Gao N, Tian X et al. Changes in cytochrome p450s-mediated drug clearance in patients with hepatocellular carcinoma in vitro and in vivo: A bottom-up approach. Oncotarget 2016, 7, 28612-28623.

Yin L, Cai Z, Zhu B, Xu C. Identification of key pathways and genes in the dynamic progression of hcc based on wgcna. Genes 2018, 9.

Yin L, Chang C, Xu C. G2/m checkpoint plays a vital role at the early stage of hcc by analysis of key pathways and genes. Oncotarget 2017, 8, 76305-76317.

Yan T, Lu L, Xie C, Chen J, Peng X, Zhu L et al. Severely impaired and dysregulated cytochrome p450 expression and activities in hepatocellular carcinoma: Implications for personalized treatment in patients. Molecular cancer therapeutics 2015, 14, 2874-2886.

Author biographies is not available.