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Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis

  • Authors:
    • Jinwei Liu
    • Zhaojin Yu
    • Mingli Sun
    • Qianqian Liu
    • Minjie Wei
    • Hua Gao
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4778-4788
    |
    Published online on: September 5, 2019
       https://doi.org/10.3892/ol.2019.10811
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Abstract

The 5‑year survival rate of hepatocellular carcinoma (HCC) is <20%; thus, identifying new potential therapeutic targets or novel biomarkers for prognosis prediction is crucial. The present study aimed to screen hub genes by constructing protein‑protein interaction (PPI) subnetworks using topological analysis methods, as well as reveal their clinical significance through big data analytics and their association with the clinicopathological features. Firstly, the PPI subnetworks were constructed using four topological analysis methods, including the MCC, DMNC, MNC and degree methods, to obtain 6 hub genes. Subsequently, the hub gene cancer/testis antigen 2 (CTAG2), which affects the prognosis of HCC (overall survival, P=0.035), was acquired by analysing clinical data in The Cancer Genome Atlas database. Meanwhile, CTAG2 expression was significantly associated with the age at diagnosis (P=0.003), T stage (P=0.028), TNM stage (P=0.028) and α‑fetoprotein (AFP) expression (P=0.045). Further immunohistochemical analysis of samples collected in our hospital revealed that the expression level of CTAG2 in 46 HCC tissues was significantly higher in comparison with that in paired adjacent tissues. The clinical data indicated that the expression of CTAG2 was significantly correlated with the hepatitis B virus status (P=0.010) and AFP expression (P=0.004). These results were then found to be consistent with the results of big data analytics. Furthermore, Gene Set Enrichment Analysis demonstrated that the function of CTAG2 in HCC may be associated with the cell cycle. Taken together, these findings suggest that CTAG2 may serve as a new potential therapeutic target for HCC patients.
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1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Perz JF, Armstrong GL, Farrington LA, Hutin YJ and Bell BP: The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 45:529–538. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Hung AK and Guy J: Hepatocellular carcinoma in the elderly: Meta-analysis and systematic literature review. World J Gastroenterol. 21:12197–12210. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Kiss A, Wang NJ, Xie JP and Thorgeirsson SS: Analysis of transforming growth factor (TGF)-alpha/epidermal growth factor receptor, hepatocyte growth Factor/c-met, TGF-beta receptor type II, and p53 expression in human hepatocellular carcinomas. Clin Cancer Res. 3:1059–1066. 1997.PubMed/NCBI

5 

Chiang DY, Villanueva A, Hoshida Y, Peix J, Newell P, Minguez B, LeBlanc AC, Donovan DJ, Thung SN, Solé M, et al: Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Res. 68:6779–6788. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Liao H, Liao M, Xu L, Yan X, Ren B, Zhu Z, Yuan K and Zeng Y: Integrative analysis of h-prune as a potential therapeutic target for hepatocellular carcinoma. EBioMedicine. 41:310–319. 2019. View Article : Google Scholar : PubMed/NCBI

7 

Jin B, Wang W, Du G, Huang GZ, Han LT, Tang ZY, Fan DG, Li J and Zhang SZ: Identifying hub genes and dysregulated pathways in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 19:592–601. 2015.PubMed/NCBI

8 

Zheng Y, Long J, Wu L, Zhang H, Li L, Zheng Y, Wang A, Lin J, Yang X, Sang X, et al: Identification of hub genes involved in the development of hepatocellular carcinoma by transcriptome sequencing. Oncotarget. 8:60358–60367. 2017.PubMed/NCBI

9 

Xiong Y, You W, Wang R, Peng L and Fu Z: prediction and validation of hub genes associated with colorectal cancer by integrating PPI network and gene expression data. BioMed Res Int. 2017:24214592017. View Article : Google Scholar : PubMed/NCBI

10 

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B and Ideker T: Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13:2498–2504. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Chin CH, Chen SH, Wu HH, Ho CW, Ko MT and Lin CY: cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 8 (Suppl 4):S112014. View Article : Google Scholar : PubMed/NCBI

12 

Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR and Winchester DP: The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more ‘personalized’ approach to cancer staging. CA Cancer J Clin. 67:93–99. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Maine EA, Westcott JM, Prechtl AM, Dang TT, Whitehurst AW and Pearson GW: The cancer-testis antigens SPANX-A/C/D and CTAG2 promote breast cancer invasion. Oncotarget. 7:14708–14726. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Han Q, Sun ML, Liu WS, Zhao HS, Jiang LY, Yu ZJ and Wei MJ: Upregulated expression of ACTL8 contributes to invasion and metastasis and indicates poor prognosis in colorectal cancer. Onco Targets Ther. 12:1749–1763. 2019. View Article : Google Scholar : PubMed/NCBI

15 

Wang J, Chen W, Wei W and Lou J: Oncogene TUBA1C promotes migration and proliferation in hepatocellular carcinoma and predicts a poor prognosis. Oncotarget. 8:96215–96224. 2017.PubMed/NCBI

16 

Wong PP, Miranda F, Chan KV, Berlato C, Hurst HC and Scibetta AG: Histone demethylase KDM5B collaborates with TFAP2C and Myc to repress the cell cycle inhibitor p21(cip) (CDKN1A). Mol Cell Biol. 32:1633–1644. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Forner A, Llovet JM and Bruix J: Hepatocellular carcinoma. Lancet. 379:1245–1255. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Wang S, Sun H, Xie Z, Li J, Hong G, Li D, Mallampati S, Zhou X, Zhou C, Zhang H, et al: Improved survival of patients with hepatocellular carcinoma and disparities by age, race and socioeconomic status by decade, 1983–2012. Oncotarget. 7:59820–59833. 2016.PubMed/NCBI

19 

Chan AC, Fan ST, Poon RT, Cheung TT, Chok KS, Chan SC and Lo CM: Evaluation of the seventh edition of the American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system for patients undergoing curative resection of hepatocellular carcinoma: Implications for the development of a refined staging system. HPB (Oxford). 15:439–448. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Greene FL and Sobin LH: The staging of cancer: A retrospective and prospective appraisal. CA Cancer J Clin. 58:180–190. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Gao H, Wang H and Yang W: Identification of key genes and construction of microRNA-mRNA regulatory networks in multiple myeloma by integrated multiple GEO datasets using bioinformatics analysis. Int J Hematol. 106:99–107. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Almeida LG, Sakabe NJ, deOliveira AR, Silva MC, Mundstein AS, Cohen T, Chen YT, Chua R, Gurung S, Gnjatic S, et al: CTdatabase: A knowledge-base of high-throughput and curated data on cancer-testis antigens. Nucleic Acids Res 37 (Database Issue). D816–D819. 2009. View Article : Google Scholar

23 

Chen YT, Scanlan MJ, Venditti CA, Chua R, Theiler G, Stevenson BJ, Iseli C, Gure AO, Vasicek T, Strausberg RL, et al: Identification of cancer/testis-antigen genes by massively parallel signature sequencing. Proc Natl Acad Sci USA. 102:7940–7945. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Caballero OL and Chen YT: Cancer/testis (CT) antigens: Potential targets for immunotherapy. Cancer Sci. 100:2014–2021. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Yao J, Caballero OL, Yung WK, Weinstein JN, Riggins GJ, Strausberg RL and Zhao Q: Tumor subtype-specific cancer-testis antigens as potential biomarkers and immunotherapeutic targets for cancers. Cancer Immunol Res. 2:371–379. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Hofmann O, Caballero OL, Stevenson BJ, Chen YT, Cohen T, Chua R, Maher CA, Panji S, Schaefer U, Kruger A, et al: Genome-wide analysis of cancer/testis gene expression. Proc Natl Acad Sci USA. 105:20422–20427. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Lotem M, Merims S, Frank S, Hamburger T, Nissan A, Kadouri L, Cohen J, Straussman R, Eisenberg G, Frankenburg S, et al: Adjuvant autologous melanoma vaccine for macroscopic stage III disease: Survival, biomarkers, and improved response to CTLA-4 blockade. J Immunol Res. 2016:81219852016. View Article : Google Scholar : PubMed/NCBI

28 

van Duin M, Broyl A, de Knegt Y, Goldschmidt H, Richardson PG, Hop WC, van der Holt B, Joseph-Pietras D, Mulligan G, Neuwirth R, et al: Cancer testis antigens in newly diagnosed and relapse multiple myeloma: Prognostic markers and potential targets for immunotherapy. Haematologica. 96:1662–1669. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Dyrskjot L, Zieger K, Kissow Lildal T, Reinert T, Gruselle O, Coche T, Borre M and Ørntoft TF: Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma. Br J Cancer. 107:116–122. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Kulkarni P, Shiraishi T, Rajagopalan K, Kim R, Mooney SM and Getzenberg RH: Cancer/testis antigens and urological malignancies. Nat Rev Urol. 9:386–396. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Shantha Kumara HM, Grieco MJ, Caballero OL, Su T, Ahmed A, Ritter E, Gnjatic S, Cekic V, Old LJ, Simpson AJ, et al: MAGE-A3 is highly expressed in a subset of colorectal cancer patients. Cancer Immu. 12:162012.

32 

Wang XY, Chen HS, Luo S, Zhang HH, Fei R and Cai J: Comparisons for detecting NY-ESO-1 mRNA expression levels in hepatocellular carcinoma tissues. Oncol Rep. 21:713–719. 2009.PubMed/NCBI

33 

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES and Mesirov JP: Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 102:15545–15550. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu J, Yu Z, Sun M, Liu Q, Wei M and Gao H: Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis. Oncol Lett 18: 4778-4788, 2019.
APA
Liu, J., Yu, Z., Sun, M., Liu, Q., Wei, M., & Gao, H. (2019). Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis. Oncology Letters, 18, 4778-4788. https://doi.org/10.3892/ol.2019.10811
MLA
Liu, J., Yu, Z., Sun, M., Liu, Q., Wei, M., Gao, H."Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis". Oncology Letters 18.5 (2019): 4778-4788.
Chicago
Liu, J., Yu, Z., Sun, M., Liu, Q., Wei, M., Gao, H."Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis". Oncology Letters 18, no. 5 (2019): 4778-4788. https://doi.org/10.3892/ol.2019.10811
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Yu Z, Sun M, Liu Q, Wei M and Gao H: Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis. Oncol Lett 18: 4778-4788, 2019.
APA
Liu, J., Yu, Z., Sun, M., Liu, Q., Wei, M., & Gao, H. (2019). Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis. Oncology Letters, 18, 4778-4788. https://doi.org/10.3892/ol.2019.10811
MLA
Liu, J., Yu, Z., Sun, M., Liu, Q., Wei, M., Gao, H."Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis". Oncology Letters 18.5 (2019): 4778-4788.
Chicago
Liu, J., Yu, Z., Sun, M., Liu, Q., Wei, M., Gao, H."Identification of cancer/testis antigen 2 gene as a potential hepatocellular carcinoma therapeutic target by hub gene screening with topological analysis". Oncology Letters 18, no. 5 (2019): 4778-4788. https://doi.org/10.3892/ol.2019.10811
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