Association between the expression of carbonic anhydrase II and clinicopathological features of hepatocellular carcinoma

  • Authors:
    • Hui Zhang
    • Changhua Zhuo
    • Dong Zhou
    • Fan Zhang
    • Minyong Chen
    • Shaohua Xu
    • Zhaoshuo Chen
  • View Affiliations

  • Published online on: April 12, 2019     https://doi.org/10.3892/ol.2019.10242
  • Pages: 5721-5728
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Abstract

The present study aimed to examine the molecular marker associated with the therapy and prognosis of hepatocellular carcinoma (HCC), and further investigate the association between its expression and the clinicopathological features of HCC. To select the core genes closely associated with HCC, differentially expressed genes (DEGs) were analyzed and screened from Gene Expression Omnibus datasets (GSE 36376) using a bioinformatics approach. Tumor and adjacent tissues were collected form 112 patients of HCC who were treated by radical resection. The expression levels of carbonic anhydrase II (CA2) in the tumor and adjacent tissues were determined using reverse transcription‑quantitative polymerase chain reaction analysis and immunohistochemistry. The χ2 test was applied for observing the association between the expression of CA2 and clinicopathological features of patients with HCC. The effects of the expression of CA2 on the patients' overall survival (OS) and disease‑free survival (DFS) were examined via Kaplan‑Meier analysis. A total of 83 DEGs were screened and analyzed using gene network analysis, among which CA2 had direct interactions with more than one disease gene of HCC. The results of immunohistochemistry showed that CA2 was expressed at a lower level in the tumor tissues compared with the adjacent tissues (t=3.012, P=0.010). Single factor analysis revealed that the mRNA expression of CA2 was able to predict the recurrence of HCC, and was significantly associated with α‑fetoprotein (AFP), microvascular invasion, tumor‑node‑metastasis (TNM) staging, and recurrence (P<0.05). The expression levels of AFP, CA2 and TNM staging were confirmed to be independent prognostic factors of HCC (P<0.05). Kaplan‑Meier analysis demonstrated that the group with a high expression of CA2 showed increased DFS and OS, compared with the low expression group (P<0.05). These findings indicated that elevated CA2 increased DFS and OS of HCC, which suggested that CA2 may be a potential target for HCC therapy.

References

1 

Kumar N, Biswas S, Mathew AE, Varghese S, Mathew JE, Nandakumar K, Aranjani JM and Lobo R: Pro-apoptotic and cytotoxic effects of enriched fraction of Elytranthe parasitica (L.) Danser against HepG2 Hepatocellular carcinoma. BMC Complement Altern Med. 16:4202016. View Article : Google Scholar : PubMed/NCBI

2 

Pan Q, Long X, Song L, Zhao D, Li X, Li D, Li M, Zhou J, Tang X, Ren H, et al: Transcriptome sequencing identified hub genes for hepatocellular carcinoma by weighted-gene co-expression analysis. Oncotarget. 7:38487–38499. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Fathy SA, Emam MA, Abo Agwa SH, Abu Zahra FA, Youssef FS and Sami RM: The antiproliferative effect of Origanum majorana on human hepatocarcinoma cell line: Suppression of NF-κB. Cell Mol Biol. 62:80–84. 2016.PubMed/NCBI

4 

Jayachandran A, Dhungel B and Steel JC: Epithelial-to-mesenchymal plasticity of cancer stem cells: Therapeutic targets in hepatocellular carcinoma. J Hematol Oncol. 9:742016. View Article : Google Scholar : PubMed/NCBI

5 

Shen J, Jiang F, Yang Y, Huang G, Pu F, Liu Q, Chen L, Ju L, Lu M, Zhou F, et al: 14-3-3η is a novel growth-promoting and angiogenic factor in hepatocellular carcinoma. J Hepatol. 65:953–962. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Zhang Y, Chen XM and Sun DL: Short-term outcomes of laparoscopic versus open right hemihepatectomy for hepatocellular carcinoma. Surg Laparosc Endosc Percutan Tech. 26:e157–e160. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Cheng S, Wei X and Wu M: Effective ways to improve the prognosis of advanced stage (BCLC stage C) hepatocellular carcinoma. Zhonghua Wai Ke Za Zhi. 53:324–327. 2015.(In Chinese). PubMed/NCBI

8 

Yang J, Jin X, Yan Y, Shao Y, Pan Y, Roberts LR, Zhang J, Huang H and Jiang J: Inhibiting histone deacetylases suppresses glucose metabolism and hepatocellular carcinoma growth by restoring FBP1 expression. Sci Rep. 7:438642017. View Article : Google Scholar : PubMed/NCBI

9 

Ehsani Ardakani MJ, Safaei A, Arefi Oskouie A, Haghparast H, Haghazali M, Mohaghegh Shalmani H, Peyvandi H, Naderi N and Zali MR: Evaluation of liver cirrhosis and hepatocellular carcinoma using Protein-Protein Interaction Networks. Gastroenterol Hepatol Bed Bench. 9 (Suppl 1):S14–S22. 2016.PubMed/NCBI

10 

Menteşe A, Erkut N, Demir S, Özer Yaman S, Sümer A, Doğramacı Ş, Alver A and Sönmez M: Autoantibodies against carbonic anhydrase I and II in patients with acute myeloid leukemia. Turk J Haematol. 34:307–313. 2017.PubMed/NCBI

11 

Sheng WW, Dong M, Zhou JP, Kong FM and Li YJ: Clinicopathological significance of the expression of carbonic anhydrase I and II in human pancreatic cancer. Zhonghua Yi Xue Za Zhi. 92:3407–3411. 2012.(In Chinese). PubMed/NCBI

12 

Viikilä P, Kivelä AJ, Mustonen H, Koskensalo S, Waheed A, Sly WS, Pastorek J, Pastorekova S, Parkkila S and Haglund C: Carbonic anhydrase enzymes II, VII, IX and XII in colorectal carcinomas. World J Gastroenterol. 22:8168–8177. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Hu X, Huang Z, Liao Z, He C and Fang X: Low CA II expression is associated with tumor aggressiveness and poor prognosis in gastric cancer patients. Int J Clin Exp Pathol. 7:6716–6724. 2014.PubMed/NCBI

14 

Järvinen P, Kivelä AJ, Nummela P, Lepistö A, Ristimäki A and Parkkila S: Carbonic anhydrase II: A novel biomarker for pseudomyxoma peritonei. APMIS. 125:207–212. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Wang Y, Jiang T, Li Z, Lu L, Zhang R, Zhang D, Wang X and Tan J: Analysis of differentially co-expressed genes based on microarray data of hepatocellular carcinoma. Neoplasma. 64:216–221. 2017. View Article : Google Scholar : PubMed/NCBI

16 

Hass HG, Vogel U, Scheurlen M and Jobst J: Gene-expression analysis identifies specific patterns of dysregulated molecular pathways and genetic subgroups of human hepatocellular carcinoma. Anticancer Res. 36:5087–5095. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Wang J, Liu F, Ao P, Li X, Zheng H, Wu D, Zhang N, She J, Yuan J and Wu X: Correlation of PDK1 expression with clinicopathologic features and prognosis of hepatocellular carcinoma. OncoTargets Ther. 9:5597–5602. 2016. View Article : Google Scholar

18 

Edge SB and Compton CC: The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

20 

Kai K, Koga H, Aishima S, Kawaguchi A, Yamaji K, Ide T, Ueda J and Noshiro H: Impact of smoking habit on surgical outcomes in non-B non-C patients with curative resection for hepatocellular carcinoma. World J Gastroenterol. 23:1397–1405. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Liang R, Lin Y, Ye JZ, Yan XX, Liu ZH, Li YQ, Luo XL and Ye HH: High expression of RBM8A predicts poor patient prognosis and promotes tumor progression in hepatocellular carcinoma. Oncol Rep. 37:2167–2176. 2017. View Article : Google Scholar : PubMed/NCBI

22 

Du Z, Niu S, Xu X and Xu Q: MicroRNA31-NDRG3 regulation axes are essential for hepatocellular carcinoma survival and drug resistance. Cancer Biomark. 19:221–230. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Li F and Liu W: Genome-wide identification, classification, and functional analysis of the basic helix-loop-helix transcription factors in the cattle, Bos Taurus. Mamm Genome. 28:176–197. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Shangguan H, Tan SY and Zhang JR: Bioinformatics analysis of gene expression profiles in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 19:2054–2061. 2015.PubMed/NCBI

25 

Liu M, Dou Y, Sun R, Zhang Y and Liu Y: Molecular mechanisms for alcoholic hepatitis based on analysis of gene expression profile. Hepat Mont. 15:e273362015.

26 

Poortahmasebi V, Poorebrahim M, Najafi S, Jazayeri SM, Alavian SM, Arab SS, Ghavami S, Alavian SE, Rezaei Moghadam A and Amiri M: How hepatitis C virus leads to hepatocellular carcinoma: A network-based study. Hepat Mont. 16:e360052016.

27 

Gokcen T, Gulcin I, Ozturk T and Goren AC: A class of sulfonamides as carbonic anhydrase I and II inhibitors. J Enzyme Inhib Med Chem. 31:180–188. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Fares M, Eladwy RA, Nocentini A, El Hadi SRA, Ghabbour HA, Abdel-Megeed A, Eldehna WM, Abdel-Aziz HA and Supuran CT: Synthesis of bulky-tailed sulfonamides incorporating pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-1(5H)-yl) moieties and evaluation of their carbonic anhydrases I, II, IV and IX inhibitory effects. Bioorg Med Chem. 25:2210–2217. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Tian MM, Fan YC, Zhao J, Gao S, Zhao ZH, Chen LY and Wang K: Hepatocellular carcinoma suppressor 1 promoter hypermethylation in serum. A diagnostic and prognostic study in hepatitis B. Clin Res Hepatol Gastroenterol. 41:171–180. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Leung TW, Tang AM, Zee B, Lau WY, Lai PB, Leung KL, Lau JT, Yu SC and Johnson PJ: Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the cancer of the liver Italian Program staging system: A study based on 926 patients. Cancer. 94:1760–1769. 2002. View Article : Google Scholar : PubMed/NCBI

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June 2019
Volume 17 Issue 6

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APA
Zhang, H., Zhuo, C., Zhou, D., Zhang, F., Chen, M., Xu, S., & Chen, Z. (2019). Association between the expression of carbonic anhydrase II and clinicopathological features of hepatocellular carcinoma. Oncology Letters, 17, 5721-5728. https://doi.org/10.3892/ol.2019.10242
MLA
Zhang, H., Zhuo, C., Zhou, D., Zhang, F., Chen, M., Xu, S., Chen, Z."Association between the expression of carbonic anhydrase II and clinicopathological features of hepatocellular carcinoma". Oncology Letters 17.6 (2019): 5721-5728.
Chicago
Zhang, H., Zhuo, C., Zhou, D., Zhang, F., Chen, M., Xu, S., Chen, Z."Association between the expression of carbonic anhydrase II and clinicopathological features of hepatocellular carcinoma". Oncology Letters 17, no. 6 (2019): 5721-5728. https://doi.org/10.3892/ol.2019.10242