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Relation of fibroblast growth factor receptor 2 expression to hepatocellular carcinoma recurrence after liver resection


Autoři: Baek Gyu Jun aff001;  Woong Cheul Lee aff002;  Jae Young Jang aff002;  Soung Won Jeong aff002;  Young Chang aff002;  Sae Hwan Lee aff003;  Young don Kim aff001;  Sang Gyune Kim aff004;  Gab Jin Cheon aff001;  Young Seok Kim aff004;  Hong Soo Kim aff003;  So Young Jin aff005
Působiště autorů: Department of Internal Medicine, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea aff001;  Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul, Korea aff002;  Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan, Korea aff003;  Department of Internal Medicine, College of Medicine, Soonchunhyang University, Bucheon, Korea aff004;  Department of Pathology, College of Medicine, Soonchunhyang University, Seoul, Korea aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227440

Souhrn

Background

Hepatocellular carcinoma (HCC) recurrence after liver resection depends upon the stage and histological grade of the tumor and the expression of certain biomarkers. However, it remains unclear which of these factors has the highest predictive value regarding HCC recurrence after surgical resection.

Methods

This study investigated the associations among clinicopathological characteristics, expression of biomarkers, and HCC recurrence after liver resection. Fifty-four patients having undergone liver resection for HCC were enrolled prospectively, and their data were analyzed retrospectively. Evaluated variables were clinical data, laboratory findings, modified Union for International Cancer Control (UICC) stage, vascular invasion, histological differentiation, and immunohistochemical staining for fibroblast growth factor receptor 2 (FGFR2), vascular endothelial growth factor, and tumor-necrosis-factor-related apoptosis-inducing ligand receptors 1 and 2.

Results

Mean patient age was 58.6 years (range, 30–71), and the mean and SD for follow-up duration were 51.2 ± 34.8 months. Cumulative 1-, 3-, and 5-year recurrence rates were 32.9%, 53.6%, and 68.1%, respectively. In univariate analysis, FGFR2 (p = 0.026) and Edmonson-Steiner grade (E-S grade) (p = 0.030) were associated with recurrence after resection in HCC patients. In multivariate analyses, increased FGFR2 expression (p = 0.017) was the only significant predictor of HCC recurrence.

Conclusions

High FGFR2 expression had marginal association with poor E-S grade (p = 0.056). More intensive surveillance of HCC recurrence is warranted in HCC patients with increased FGFR2 expression.

Klíčová slova:

Biomarkers – Cirrhosis – Fibroblast growth factor – Hepatic resection – Hepatocellular carcinoma – Histology – Immune receptors – Surgical resection


Zdroje

1. Bruix J, Sherman M, American Association for the Study of Liver D. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2. doi: 10.1002/hep.24199 21374666

2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: a cancer journal for clinicians. 2011;61(2):69–90.

3. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362(9399):1907–17. doi: 10.1016/S0140-6736(03)14964-1 14667750

4. Rahbari NN, Mehrabi A, Mollberg NM, Muller SA, Koch M, Buchler MW, et al. Hepatocellular carcinoma: current management and perspectives for the future. Annals of surgery. 2011;253(3):453–69. doi: 10.1097/SLA.0b013e31820d944f 21263310

5. Llovet JM, Schwartz M, Mazzaferro V. Resection and liver transplantation for hepatocellular carcinoma. Seminars in liver disease. 2005;25(2):181–200. doi: 10.1055/s-2005-871198 15918147

6. Kobayashi A, Kawasaki S, Miyagawa S, Miwa S, Noike T, Takagi S, et al. Results of 404 hepatic resections including 80 repeat hepatectomies for hepatocellular carcinoma. Hepato-gastroenterology. 2006;53(71):736–41. 17086879

7. Minagawa M, Makuuchi M, Takayama T, Kokudo N. Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma. Annals of surgery. 2003;238(5):703–10. doi: 10.1097/01.sla.0000094549.11754.e6 14578733

8. Poon RT, Fan ST, Lo CM, Ng IO, Liu CL, Lam CM, et al. Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years. Annals of surgery. 2001;234(1):63–70. doi: 10.1097/00000658-200107000-00010 11420484

9. Taura K, Ikai I, Hatano E, Fujii H, Uyama N, Shimahara Y. Implication of frequent local ablation therapy for intrahepatic recurrence in prolonged survival of patients with hepatocellular carcinoma undergoing hepatic resection: an analysis of 610 patients over 16 years old. Annals of surgery. 2006;244(2):265–73. doi: 10.1097/01.sla.0000217921.28563.55 16858190

10. Behne T, Copur MS. Biomarkers for hepatocellular carcinoma. International journal of hepatology. 2012;2012.

11. Lee SH, Lee JS, Na GH, You YK, Kim DG. Immunohistochemical markers for hepatocellular carcinoma prognosis after liver resection and liver transplantation. Clinical transplantation. 2017;31(1):e12852.

12. Mocchetti I, Spiga G, Hayes VY, Isackson PJ, Colangelo A. Glucocorticoids differentially increase nerve growth factor and basic fibroblast growth factor expression in the rat brain. The Journal of neuroscience: the official journal of the Society for Neuroscience. 1996;16(6):2141–8.

13. Yasumoto H, Matsubara A, Mutaguchi K, Usui T, McKeehan WL. Restoration of fibroblast growth factor receptor2 suppresses growth and tumorigenicity of malignant human prostate carcinoma PC-3 cells. The Prostate. 2004;61(3):236–42. doi: 10.1002/pros.20093 15368475

14. Naimi B, Latil A, Fournier G, Mangin P, Cussenot O, Berthon P. Down-regulation of (IIIb) and (IIIc) isoforms of fibroblast growth factor receptor 2 (FGFR2) is associated with malignant progression in human prostate. The Prostate. 2002;52(3):245–52. doi: 10.1002/pros.10104 12111699

15. Ricol D, Cappellen D, El Marjou A, Gil-Diez-de-Medina S, Girault JM, Yoshida T, et al. Tumour suppressive properties of fibroblast growth factor receptor 2-IIIb in human bladder cancer. Oncogene. 1999;18(51):7234–43. doi: 10.1038/sj.onc.1203186 10602477

16. Gartside MG, Chen H, Ibrahimi OA, Byron SA, Curtis AV, Wellens CL, et al. Loss-of-function fibroblast growth factor receptor-2 mutations in melanoma. Molecular cancer research: MCR. 2009;7(1):41–54. doi: 10.1158/1541-7786.MCR-08-0021 19147536

17. Harimoto N, Taguchi K, Shirabe K, Adachi E, Sakaguchi Y, Toh Y, et al. The significance of fibroblast growth factor receptor 2 expression in differentiation of hepatocellular carcinoma. Oncology. 2010;78(5–6):361–8. doi: 10.1159/000320463 20798558

18. Poon RT, Lau C, Yu WC, Fan ST, Wong J. High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: a prospective study. Oncology reports. 2004;11(5):1077–84. 15069550

19. Johnstone RW, Frew AJ, Smyth MJ. The TRAIL apoptotic pathway in cancer onset, progression and therapy. Nat Rev Cancer. 2008;8(10):782–98. doi: 10.1038/nrc2465 18813321

20. Eichhorst ST. Modulation of apoptosis as a target for liver disease. Expert Opin Ther Targets. 2005;9(1):83–99. doi: 10.1517/14728222.9.1.83 15757484

21. Llovet JM. Updated treatment approach to hepatocellular carcinoma. Journal of gastroenterology. 2005;40(3):225–35. doi: 10.1007/s00535-005-1566-3 15830281

22. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. The New England journal of medicine. 1996;334(11):693–9. doi: 10.1056/NEJM199603143341104 8594428

23. Liver Cancer Study Group of Japan. The general rules for the clinical and pathological study of primary liver cancer. 4th ed. Tokyo: Kanehara and Co. Ltd.

24. Minagawa M, Ikai I, Matsuyama Y, Yamaoka Y, Makuuchi M. Staging of hepatocellular carcinoma: assessment of the Japanese TNM and AJCC/UICC TNM systems in a cohort of 13,772 patients in Japan. Annals of surgery. 2007;245(6):909–22. doi: 10.1097/01.sla.0000254368.65878.da 17522517

25. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. Journal of hepatology. 1995;22(6):696–9. doi: 10.1016/0168-8278(95)80226-6 7560864

26. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21. doi: 10.1002/hep.20701 15915461

27. Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. Journal of hepatology. 2003;38(2):200–7. doi: 10.1016/s0168-8278(02)00360-4 12547409

28. Yamamoto Y, Ikoma H, Morimura R, Konishi H, Murayama Y, Komatsu S, et al. Optimal duration of the early and late recurrence of hepatocellular carcinoma after hepatectomy. World journal of gastroenterology: WJG. 2015;21(4):1207. doi: 10.3748/wjg.v21.i4.1207 25632194

29. Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. Journal of the National Cancer Institute. 2008;100(10):698–711. doi: 10.1093/jnci/djn134 18477802

30. Ridyard MS, Robbins SM. Fibroblast growth factor-2-induced signaling through lipid raft-associated fibroblast growth factor receptor substrate 2 (FRS2). The Journal of biological chemistry. 2003;278(16):13803–9. doi: 10.1074/jbc.M210245200 12571252

31. Hu Z, Evarts RP, Fujio K, Marsden ER, Thorgeirsson SS. Expression of fibroblast growth factor receptors flg and bek during hepatic ontogenesis and regeneration in the rat. Cell growth & differentiation: the molecular biology journal of the American Association for Cancer Research. 1995;6(8):1019–25.

32. Asada N, Tanaka Y, Hayashido Y, Toratani S, Kan M, Kitamoto M, et al. Expression of fibroblast growth factor receptor genes in human hepatoma-derived cell lines. In vitro cellular & developmental biology Animal. 2003;39(7):321–8.

33. Niizeki T, Sumie S, Torimura T, Kurogi J, Kuromatsu R, Iwamoto H, et al. Serum vascular endothelial growth factor as a predictor of response and survival in patients with advanced hepatocellular carcinoma undergoing hepatic arterial infusion chemotherapy. Journal of gastroenterology. 2012;47(6):686–95. doi: 10.1007/s00535-012-0555-6 22382631

34. Kriegl L, Jung A, Engel J, Jackstadt R, Gerbes AL, Gallmeier E, et al. Expression, cellular distribution, and prognostic relevance of TRAIL receptors in hepatocellular carcinoma. Clinical cancer research: an official journal of the American Association for Cancer Research. 2010;16(22):5529–38.

35. Jang JY, Shao RX, Lin W, Weinberg E, Chung WJ, Tsai WL, et al. HIV infection increases HCV-induced hepatocyte apoptosis. J Hepatol. 2011;54(4):612–20. doi: 10.1016/j.jhep.2010.07.042 21146890


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