Exploring The Mechanism of Postoperative Recurrence of Hepatocellular Carcinoma and Predicting The Candidate Drugs_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 SUNXiao-guo , LILi , WANGJin-hua

Department of General Surgery, Tai'an First People's Hospital of Shandong Province, Tai'an 271000, Shandong Province, China;

Corresponding author：

SUNXiao-guo, Email: xiaoguosun@163.com

Keywords：

Hepatocellular carcinoma; Postoperative recurrence; Molecular mechanism; Drug; Gene set enrichment analysis

DOI：

10.7507/1007-9424.20140298

Video：

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Objective To explore the mechanism of postoperative recurrence of hepatocellular carcinoma(HCC) and predicting the candidate drug. Methods The differently expressed genes of the human gene expression profiles with 35 postoperative recurrence of HCC tissues and 41 no recurrence of HCC tissues were identified. Then enriched these genes with gene ontology(GO) terms and KEGG pathway, and predicting the candidate drugs for suppress the postoperative recurrence using Connectivity Map(cmap) database. Results Several pathways such as Focal adhesion and MAPK signaling pathway were found involve in postoperative recurrence of HCC. Moreover, two candidate small molecule drugs(bambuterol and lovastatin) were found may suppress and postoperative recurrence of HCC. Conclusion Focal adhesion and MAPK signaling pathway may involve in the postoperative recurrence of HCC, bambuterol and lovastatin may candidate drugs for treat postoperative recurrence of HCC.

Citation： SUNXiao-guo, LILi, WANGJin-hua. Exploring The Mechanism of Postoperative Recurrence of Hepatocellular Carcinoma and Predicting The Candidate Drugs. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(10): 1245-1249. doi: 10.7507/1007-9424.20140298 Copy

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1. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma[J]. Lancet, 2003, 362(9399):1907-1917.
2. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis:from genes to environment[J]. Nature Rev Cancer, 2006, 6(9):674-687.
3. El-Serag HB, Rudolph KL. Hepatocellular carcinoma:epidemiology and molecular carcinogenesis[J]. Gastroenterology, 2007, 132(7):2557-2576.
4. Poon D, Anderson BO, Chen LT, et al. Management of hepatocellular carcinoma in Asia:consensus statement from the Asian Oncology Summit[J]. Lancet Oncol, 2009, 10(11):1111-1118.
5. Bruix J, Sherman M. Practice Guide lines Committee, American Association for the Study of Liver Diseases. Management of hepa tocellular carcinoma[J]. Hepatology, 2005, 42(5):1208-36.
6. Poon TP, Fan ST, Wong J. Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma[J]. Ann Surg, 2000, 232(1):10-24.
7. Portolani N, Coniglio A, Ghidoni S, et al. Early and late recurrence after liver resection for hepatocellular carcinoma:prognostic and therapeutic implications[J]. Ann Surg, 2006, 243(2):229-235.
8. Wang SM, Ooi LL, Hui KM. Upregulation of Rac GTPase-activating protein 1 is significantly associated with the early recurrence of human hepatocellular carcinoma[J]. Clin Cancer Res, 2011, 17(18):6040-6051.
9. Futreal PA, Coin L, Marshall M, et al. A census of human cancer genes[J]. Nature reviews, 2004, 4(3):177-183.
10. Maere S, Heymans K, Kuiper M. BiNGO:a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks[J]. Bioinformatics, 2005, 21(16):3448-3449.
11. Xie C, Mao X, Huang J, et al. KOBAS 2.0:a web server for annotation and identification of enriched pathways and diseases[J]. Nucleic Acids Res, 2011, 39(Web Server issue):W316-W322.
12. Lamb J, Crawford ED, Peck D, et al. The Connectivity Map:using gene-expression signatures to connect small molecules, genes, and disease[J]. Science, 2006, 313(5795):1929-1935.
13. Zaman SN, Johnson RD, Johnson PJ, et al. Risk factors in development of hepatocellular carcinoma in cirrhosis:prospective study of 613 patients[J]. Lancet, 1985, 1(8442):1357-1360.
14. Tsukuma H, Hiyama T, Tanaka S, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease[J]. N Engl J Med, 1993, 328(25):1797-1801.
15. Bolondi L, Sofia S, Siringo S, et al. Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma:a cost effectiveness analysis[J]. Gut, 2001, 48(2):251-259.
16. Yeh FS, Yu MC, MoC C, et al. Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi China[J]. Cancer Res, 1989, 49(9):2506-2509.
17. Thomas MB, ZhuAX. Hepatocellular carcinoma:the need for progress[J]. J Clin Oncol, 2005, 23(13):2892-2899.
18. Lin YM, Chang JH, Yeh KT, et al. Disturbance of circadian gene expression in hepatocellular Carcinoma[J]. Mol Carcinog, 2008, 47(12):925-933.
19. Jiang R, Tan Z, Deng L, et al. Interleukin-22 promotes human hepatocellular carcinoma by activation of STAT3[J]. Hepato-logy, 2011, 54(3):900-909.
20. Zhou Q, Lui VW, Yeo W. Targeting the PI3K/Akt/mTOR pathway in hepatocellular carcinoma[J]. Future Oncol, 2011, 7(10):1149-1167.
21. Hanahan D, Weinberg RA. Hallmarks of cancer:the next generation[J]. Cell, 144(5):646-674.
22. Martirosyan A, Clendening JW, Goard CA, et al. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin:potential therapeutic relevance[J]. BMC Cancer, 2010, 10:103.
23. Sanli T, Liu C, Rashid A, et al. Lovastatin sensitizes lung cancer cells to ionizing radiation:modulation of molecular pathways of radioresistance and tumor suppression[J]. J Thorac Oncol, 2011, 6(3):439-450.
24. Xu W, Lacerda L, Debeb BG, et al. The antihelmintic drug pyrvinium pamoate targets aggressive breast cancer[J]. PLoS One, 2013, 8(8):e71508.
25. Deng L, Lei Y, Liu R, et al. Pyrvinium targets autophagy addic tion to promote cancer cell death[J]. Cell Death Dis, 2013, 4:e614.
26. Fainstein V, Bodey GP, Bolivar R, et al. Moxalactam plus ticarcillin or tobramycin for treatment of febrile episodes in neutropenic cancer patients[J]. Arch Intern Med, 1984, 144(9):1766-1770.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Exploring The Mechanism of Postoperative Recurrence of Hepatocellular Carcinoma and Predicting The Candidate Drugs

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