Skip to main content
Top
Published in: Pathology & Oncology Research 4/2015

Open Access 01-09-2015 | Research

Exploring the Molecular Mechanism and Biomakers of Liver Cancer Based on Gene Expression Microarray

Authors: Pengfei Liu, Wenhua Jiang, He Ren, Huilai Zhang, Jihui Hao

Published in: Pathology & Oncology Research | Issue 4/2015

Login to get access

Abstract

Liver cancer is one of the most common cancers worldwide with high morbidity and mortality. Its molecular mechanism hasn’t been fully understood though many studies have been conducted and thus further researches are still needed to improve the prognosis of liver cancer. Firstly, differentially expressed genes (DEGs) between six Mdr2-knockout (Mdr2-KO) mutant mice samples (3-month-old and 12-month-old) and six control mice samples were identified. Then, the enriched GO terms and KEGG pathways of those DEGs were obtained using the Database for Annotation, Visualization and Integrated Discovery (DAVID, http://​david.​abcc.​ncifcrf.​gov/​). Finally, protein-protein interactions (PPI) network of those DEGs were constructed using STRING database (http://​www.​string-db.​org/​) and visualized by Cytoscape software, at the same time, genes with high degree were selected out. Several novel biomarkers that might play important roles in liver cancer were identified through the analysis of gene microarray in GEO. Also, some genes such as Tyrobp, Ctss and pathways such as Pathways in cancer, ECM-receptor interaction that had been researched previously were further confirmed in this study. Through the bioinformatics analysis of the gene microarray in GEO, we found some novel biomarkers of liver cancer and further confirmed some known biomarkers.
Literature
1.
go back to reference Bertino G, Demma S, Ardiri A, Proiti M, Gruttadauria S, Toro A, Malaguarnera G, Bertino N, Malaguarnera M, Di Carlo I (2014) Hepatocellular carcinoma: novel molecular targets in carcinogenesis for future therapies. Biomed Res Int 2014, 203693PubMedCentralCrossRefPubMed Bertino G, Demma S, Ardiri A, Proiti M, Gruttadauria S, Toro A, Malaguarnera G, Bertino N, Malaguarnera M, Di Carlo I (2014) Hepatocellular carcinoma: novel molecular targets in carcinogenesis for future therapies. Biomed Res Int 2014, 203693PubMedCentralCrossRefPubMed
2.
go back to reference JianXin J, Cha Y, ZhiPeng L, Jie X, Hao Z, Meiyuan C, ChengYi S (2014) GOLP3 is a predictor of survival in patients with hepatocellular carcinoma. Clin Invest Med 37(4):E233PubMed JianXin J, Cha Y, ZhiPeng L, Jie X, Hao Z, Meiyuan C, ChengYi S (2014) GOLP3 is a predictor of survival in patients with hepatocellular carcinoma. Clin Invest Med 37(4):E233PubMed
3.
go back to reference Mah WC, Thurnherr T, Chow PK, Chung AY, Ooi LL, Toh HC, Teh BT, Saunthararajah Y, Lee CG (2014) Methylation profiles reveal distinct subgroup of hepatocellular carcinoma patients with poor prognosis. PLoS One 9(8):e104158PubMedCentralCrossRefPubMed Mah WC, Thurnherr T, Chow PK, Chung AY, Ooi LL, Toh HC, Teh BT, Saunthararajah Y, Lee CG (2014) Methylation profiles reveal distinct subgroup of hepatocellular carcinoma patients with poor prognosis. PLoS One 9(8):e104158PubMedCentralCrossRefPubMed
4.
go back to reference Smit JJ, Schinkel AH, Oude Elferink RP, Groen AK, Wagenaar E, van Deemter L, Mol CA, Ottenhoff R, van der Lugt NM, van Roon MA et al (1993) Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75(3):451–462CrossRefPubMed Smit JJ, Schinkel AH, Oude Elferink RP, Groen AK, Wagenaar E, van Deemter L, Mol CA, Ottenhoff R, van der Lugt NM, van Roon MA et al (1993) Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75(3):451–462CrossRefPubMed
5.
go back to reference Katzenellenbogen M, Mizrahi L, Pappo O, Klopstock N, Olam D, Barash H, Domany E, Galun E, Goldenberg D (2007) Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma development in Mdr2 knockout mice. Mol Cancer Ther 6(4):1283–1291CrossRefPubMed Katzenellenbogen M, Mizrahi L, Pappo O, Klopstock N, Olam D, Barash H, Domany E, Galun E, Goldenberg D (2007) Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma development in Mdr2 knockout mice. Mol Cancer Ther 6(4):1283–1291CrossRefPubMed
6.
go back to reference Yang YM, Lee WH, Lee CG, An J, Kim ES, Kim SH, Lee SK, Lee CH, Dhanasekaran DN, Moon A, Hwang S, Lee SJ, Park JW, Kim KM, Kim SG (2014) Galpha gep oncogene deregulation of p53-responsive microRNAs promotes epithelial-mesenchymal transition of hepatocellular carcinoma. Oncogene 0 Yang YM, Lee WH, Lee CG, An J, Kim ES, Kim SH, Lee SK, Lee CH, Dhanasekaran DN, Moon A, Hwang S, Lee SJ, Park JW, Kim KM, Kim SG (2014) Galpha gep oncogene deregulation of p53-responsive microRNAs promotes epithelial-mesenchymal transition of hepatocellular carcinoma. Oncogene 0
8.
go back to reference Katzenellenbogen M, Pappo O, Barash H, Klopstock N, Mizrahi L, Olam D, Jacob-Hirsch J, Amariglio N, Rechavi G, Mitchell LA, Kohen R, Domany E, Galun E, Goldenberg D (2006) Multiple adaptive mechanisms to chronic liver disease revealed at early stages of liver carcinogenesis in the Mdr2-knockout mice. Cancer Res 66(8):4001–4010CrossRefPubMed Katzenellenbogen M, Pappo O, Barash H, Klopstock N, Mizrahi L, Olam D, Jacob-Hirsch J, Amariglio N, Rechavi G, Mitchell LA, Kohen R, Domany E, Galun E, Goldenberg D (2006) Multiple adaptive mechanisms to chronic liver disease revealed at early stages of liver carcinogenesis in the Mdr2-knockout mice. Cancer Res 66(8):4001–4010CrossRefPubMed
9.
go back to reference Gautier L, Cope L, Bolstad BM, Irizarry RA (2004) Affy–analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3):307–315CrossRefPubMed Gautier L, Cope L, Bolstad BM, Irizarry RA (2004) Affy–analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3):307–315CrossRefPubMed
10.
go back to reference Diboun I, Wernisch L, Orengo CA, Koltzenburg M (2006) Microarray analysis after RNA amplification can detect pronounced differences in gene expression using limma. BMC Genomics 7:252PubMedCentralCrossRefPubMed Diboun I, Wernisch L, Orengo CA, Koltzenburg M (2006) Microarray analysis after RNA amplification can detect pronounced differences in gene expression using limma. BMC Genomics 7:252PubMedCentralCrossRefPubMed
11.
go back to reference Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504PubMedCentralCrossRefPubMed Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504PubMedCentralCrossRefPubMed
12.
go back to reference Chefetz I, Alvero AB, Holmberg JC, Lebowitz N, Craveiro V, Yang-Hartwich Y, Yin G, Squillace L, Gurrea Soteras M, Aldo P, Mor G (2013) TLR2 enhances ovarian cancer stem cell self-renewal and promotes tumor repair and recurrence. Cell Cycle 12(3):511–521PubMedCentralCrossRefPubMed Chefetz I, Alvero AB, Holmberg JC, Lebowitz N, Craveiro V, Yang-Hartwich Y, Yin G, Squillace L, Gurrea Soteras M, Aldo P, Mor G (2013) TLR2 enhances ovarian cancer stem cell self-renewal and promotes tumor repair and recurrence. Cell Cycle 12(3):511–521PubMedCentralCrossRefPubMed
13.
go back to reference Usami Y, Ishida K, Sato S, Kishino M, Kiryu M, Ogawa Y, Okura M, Fukuda Y, Toyosawa S (2013) Intercellular adhesion molecule-1 (ICAM-1) expression correlates with oral cancer progression and induces macrophage/cancer cell adhesion. Int J Cancer 133(3):568–578CrossRefPubMed Usami Y, Ishida K, Sato S, Kishino M, Kiryu M, Ogawa Y, Okura M, Fukuda Y, Toyosawa S (2013) Intercellular adhesion molecule-1 (ICAM-1) expression correlates with oral cancer progression and induces macrophage/cancer cell adhesion. Int J Cancer 133(3):568–578CrossRefPubMed
14.
go back to reference Ciftci R, Tas F, Yasasever CT, Aksit E, Karabulut S, Sen F, Keskin S, Kilic L, Yildiz I, Bozbey HU, Duranyildiz D, Vatansever S (2014) High serum transforming growth factor beta 1 (TGFB1) level predicts better survival in breast cancer. Tumour Biol 35(7):6941–6948CrossRefPubMed Ciftci R, Tas F, Yasasever CT, Aksit E, Karabulut S, Sen F, Keskin S, Kilic L, Yildiz I, Bozbey HU, Duranyildiz D, Vatansever S (2014) High serum transforming growth factor beta 1 (TGFB1) level predicts better survival in breast cancer. Tumour Biol 35(7):6941–6948CrossRefPubMed
15.
go back to reference Liu YY, Han JY, Lin SC, Liu ZY, Jiang WT (2014) Effect of CDH1 gene methylation on transforming growth factor (TGF-beta)-induced epithelial-mesenchymal transition in alveolar epithelial cell line A549. Genet Mol Res 13(4):8568–8576 Liu YY, Han JY, Lin SC, Liu ZY, Jiang WT (2014) Effect of CDH1 gene methylation on transforming growth factor (TGF-beta)-induced epithelial-mesenchymal transition in alveolar epithelial cell line A549. Genet Mol Res 13(4):8568–8576
16.
go back to reference Huang CY, Fong YC, Lee CY, Chen MY, Tsai HC, Hsu HC, Tang CH (2009) CCL5 increases lung cancer migration via PI3K, Akt and NF-kappaB pathways. Biochem Pharmacol 77(5):794–803CrossRefPubMed Huang CY, Fong YC, Lee CY, Chen MY, Tsai HC, Hsu HC, Tang CH (2009) CCL5 increases lung cancer migration via PI3K, Akt and NF-kappaB pathways. Biochem Pharmacol 77(5):794–803CrossRefPubMed
17.
go back to reference Leavy O (2014) Innate immune signalling: TIRAP diversifies the sites of TLR signalling. Nat Rev Immunol 14(4):211CrossRefPubMed Leavy O (2014) Innate immune signalling: TIRAP diversifies the sites of TLR signalling. Nat Rev Immunol 14(4):211CrossRefPubMed
18.
go back to reference Medeiros MC, Frasnelli SC, Bastos Ade S, Orrico SR, Rossa C (2014) Modulation of cell proliferation, survival and gene expression by RAGE and TLR signaling in cells of the innate and adaptive immune response: role of p38 MAPK and NF-KB. J Appl Oral Sci 22(3):185–193PubMedCentralCrossRefPubMed Medeiros MC, Frasnelli SC, Bastos Ade S, Orrico SR, Rossa C (2014) Modulation of cell proliferation, survival and gene expression by RAGE and TLR signaling in cells of the innate and adaptive immune response: role of p38 MAPK and NF-KB. J Appl Oral Sci 22(3):185–193PubMedCentralCrossRefPubMed
19.
go back to reference Kos J, Sekirnik A, Kopitar G, Cimerman N, Kayser K, Stremmer A, Fiehn W, Werle B (2001) Cathepsin S in tumours, regional lymph nodes and sera of patients with lung cancer: relation to prognosis. Br J Cancer 85(8):1193–1200PubMedCentralCrossRefPubMed Kos J, Sekirnik A, Kopitar G, Cimerman N, Kayser K, Stremmer A, Fiehn W, Werle B (2001) Cathepsin S in tumours, regional lymph nodes and sera of patients with lung cancer: relation to prognosis. Br J Cancer 85(8):1193–1200PubMedCentralCrossRefPubMed
20.
go back to reference Lee TK, Cheung VC, Lu P, Lau EY, Ma S, Tang KH, Tong M, Lo J, Ng IO (2014) Blockade of CD47-mediated cathepsin S/protease-activated receptor 2 signaling provides a therapeutic target for hepatocellular carcinoma. Hepatology 60(1):179–191CrossRefPubMed Lee TK, Cheung VC, Lu P, Lau EY, Ma S, Tang KH, Tong M, Lo J, Ng IO (2014) Blockade of CD47-mediated cathepsin S/protease-activated receptor 2 signaling provides a therapeutic target for hepatocellular carcinoma. Hepatology 60(1):179–191CrossRefPubMed
21.
go back to reference Shabo I, Svanvik J (2011) Expression of macrophage antigens by tumor cells. Adv Exp Med Biol 714:141–150CrossRefPubMed Shabo I, Svanvik J (2011) Expression of macrophage antigens by tumor cells. Adv Exp Med Biol 714:141–150CrossRefPubMed
22.
go back to reference Shabo I, Olsson H, Stal O, Svanvik J (2013) Breast cancer expression of DAP12 is associated with skeletal and liver metastases and poor survival. Clin Breast Cancer 13(5):371–377CrossRefPubMed Shabo I, Olsson H, Stal O, Svanvik J (2013) Breast cancer expression of DAP12 is associated with skeletal and liver metastases and poor survival. Clin Breast Cancer 13(5):371–377CrossRefPubMed
23.
go back to reference Costa VL, Henrique R, Danielsen SA, Duarte-Pereira S, Eknaes M, Skotheim RI, Rodrigues A, Magalhaes JS, Oliveira J, Lothe RA, Teixeira MR, Jeronimo C, Lind GE (2010) Three epigenetic biomarkers, GDF15, TMEFF2, and VIM, accurately predict bladder cancer from DNA-based analyses of urine samples. Clin Cancer Res 16(23):5842–5851CrossRefPubMed Costa VL, Henrique R, Danielsen SA, Duarte-Pereira S, Eknaes M, Skotheim RI, Rodrigues A, Magalhaes JS, Oliveira J, Lothe RA, Teixeira MR, Jeronimo C, Lind GE (2010) Three epigenetic biomarkers, GDF15, TMEFF2, and VIM, accurately predict bladder cancer from DNA-based analyses of urine samples. Clin Cancer Res 16(23):5842–5851CrossRefPubMed
Metadata
Title
Exploring the Molecular Mechanism and Biomakers of Liver Cancer Based on Gene Expression Microarray
Authors
Pengfei Liu
Wenhua Jiang
He Ren
Huilai Zhang
Jihui Hao
Publication date
01-09-2015
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 4/2015
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-015-9926-7

Other articles of this Issue 4/2015

Pathology & Oncology Research 4/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine