Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Roles of Fibroblast Growth Factor-inducible 14 in Hepatocellular Carcinoma

  • Li, Nan (Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University) ;
  • Hu, Wen-Jun (Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University) ;
  • Shi, Jie (Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University) ;
  • Xue, Jie (Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University) ;
  • Guo, Wei-Xing (Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University) ;
  • Zhang, Yang (Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University) ;
  • Guan, Dong-Xian (Institute of Nutrition and Metabolism, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) ;
  • Liu, Shu-Peng (Changhai Hospital, The Second Military Medical University) ;
  • Cheng, Yu-Qiang (Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University) ;
  • Wu, Meng-Chao (Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University) ;
  • Xie, Dong (Institute of Nutrition and Metabolism, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) ;
  • Liu, Shan-Rong (Changhai Hospital, The Second Military Medical University) ;
  • Cheng, Shu-Qun (Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University)
  • Published : 2013.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The prognostic value of the fibroblast growth factor-inducible 14 (Fn14) expression in hepatocellular carcinoma (HCC) is unknown. Real-time PCR (RT-PCR), western blot assays and immunohistochemistry analysis were here performed in order to compare Fn14 expressios in paired liver samples of HCC and normal liver tissue. Most of the tumor tissues expressed significantly higher levels of Fn14 compared to adjacent non-tumor tissues, with Fn14High accounting for 54.6% (142/260) of all patients. The Pearson ${\chi}^2$ test indicated that Fn14 expression was closely associated with serum alpha fetal protein (AFP) (P=0.002) and tumor number (p=0.019). Univariate and multivariate analyses revealed that along with tumor diameter and portal vein tumor thrombosis (PVTT ) type, Fn14 was an independent prognostic factor for both overall survival (OS) (HR=1.398, p=0.008) and recurrence (HR=1.541, p=0.001) rates. Fn14 overexpression HCC correlated with poor surgical outcome, and this molecule may be a candidate biomarker for prognosis as well as a target for therapy.

Keywords

References

  1. Ando T, Ichikawa J, Wako M, et al (2006). TWEAK/Fn14 interaction regulates RANTES production, BMP-2-induced differentiation, and RANKL expression in mouse osteoblastic MC3T3-E1 cells. Arthritis Res Ther, 8, R146. https://doi.org/10.1186/ar2038
  2. Asrani K, Keri RA, Galisteo R, et al (2013). The HER2- and Heregulin beta1 (HRG)-inducible TNFR Superfamily Member Fn14 Promotes HRG-driven Cell Migration, Invasion and MMP9 Expression. Mol Cancer Res, 11, 393-404. https://doi.org/10.1158/1541-7786.MCR-12-0542
  3. Bridges JF, Joy SM, Gallego G, et al (2011). Needs for hepatocellular carcinoma control policy in the Asia-Pacific region. Asian Pac J Cancer Prev, 12, 2585-91.
  4. Brown SA, Richards CM, Hanscom H N, et al (2003). The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation. Biochem J, 371, 395-403. https://doi.org/10.1042/BJ20021730
  5. Bruix J, Sherman M (2005). Management of hepatocellular carcinoma. Hepatology, 42, 1208-36. https://doi.org/10.1002/hep.20933
  6. Dai Z, Liu YK, Cui JF, et al (2006). Identification and analysis of altered alpha1, 6-fucosylated glycoproteins associated with hepatocellular carcinoma metastasis. Proteomics, 6, 5857-67. https://doi.org/10.1002/pmic.200500707
  7. Feng SL, Guo Y, Factor VM, et al (2000). The Fn14 immediateearly response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas. Am J Pathol, 156, 1253-61. https://doi.org/10.1016/S0002-9440(10)64996-6
  8. Gu L, Dai L, Cao C, et al (2013). Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention. PLoS One, 8, e57436. https://doi.org/10.1371/journal.pone.0057436
  9. Han H, Bearss DJ, Browne LW, et al (2002). Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray. Cancer Res, 62, 2890-6.
  10. Kawakita T, Shiraki K, Yamanaka Y, et al (2005). Functional expression of TWEAK in human colonic adenocarcinoma cells. Int J Oncol, 26, 87-93.
  11. Li H, Hu Y, Li N, Zhou Y (2012). Liver fibrosis and five year survival of hepatocellular cancer cases undergoing transcatheter arterial chemo embolization using small doses. Asian Pac J Cancer Prev, 13, 1589-93. https://doi.org/10.7314/APJCP.2012.13.4.1589
  12. Li L, Yu C, Gao H, Li Y (2010). Argonaute proteins: potential biomarkers for human colon cancer. BMC Cancer, 10, 38. https://doi.org/10.1186/1471-2407-10-38
  13. Llovet JM, Di Bisceglie AM, Bruix J, et al (2008). Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst, 100, 698-711. https://doi.org/10.1093/jnci/djn134
  14. Meighan-Mantha RL, Hsu DK, Guo Y, et al (1999). The mitogeninducible Fn14 gene encodes a type I transmembrane protein that modulates fibroblast adhesion and migration. J Biol Chem, 274, 33166-76. https://doi.org/10.1074/jbc.274.46.33166
  15. Michaelson JS, Burkly LC (2009). Therapeutic targeting of TWEAK/Fnl4 in cancer: exploiting the intrinsic tumor cell killing capacity of the pathway. Results Probl Cell Differ, 49, 145-60. https://doi.org/10.1007/400_2008_18
  16. Michaelson JS, Cho S, Browning B, et al (2005). Tweak induces mammary epithelial branching morphogenesis. Oncogene, 24, 2613-24. https://doi.org/10.1038/sj.onc.1208208
  17. Poon RT, Ng IO, Lau C, et al (2002). Tumor microvessel density as a predictor of recurrence after resection of hepatocellular carcinoma: a prospective study. J Clin Oncol, 20, 1775-85. https://doi.org/10.1200/JCO.2002.07.089
  18. Saitoh T, Nakayama M, Nakano H, et al (2003). TWEAK induces NF-kappaB2 p100 processing and long lasting NF-kappaB activation. J Biol Chem, 278, 36005-12. https://doi.org/10.1074/jbc.M304266200
  19. Shi J, Lai EC, Li N, et al (2010). Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus. Ann Surg Oncol, 17, 2073-80. https://doi.org/10.1245/s10434-010-0940-4
  20. Tirnitz-Parker JE, Viebahn CS, Jakubowski A, et al (2010). Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells. Hepatology, 52, 291-302. https://doi.org/10.1002/hep.23663
  21. Tran NL, McDonough WS, Donohue PJ, et al (2003). The human Fn14 receptor gene is up-regulated in migrating glioma cells in vitro and overexpressed in advanced glial tumors. Am J Pathol, 162, 1313-21. https://doi.org/10.1016/S0002-9440(10)63927-2
  22. Tran NL, McDonough WS, Savitch BA, et al (2005). The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)-fibroblast growth factor-inducible 14 (Fn14) signaling system regulates glioma cell survival via NFkappaB pathway activation and BCL-XL/BCL-W expression. J Biol Chem, 280, 3483-92. https://doi.org/10.1074/jbc.M409906200
  23. Tran NL, McDonough WS, Savitch BA, et al (2006). Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Cancer Res, 66, 9535-42. https://doi.org/10.1158/0008-5472.CAN-06-0418
  24. Wang J, Liu Y, Wei MJ, et al (2013). Clinical correlations and prognostic relevance of Fn14 expression in breast carcinoma. Histol Histopathol.
  25. Wang S, Jiang W, Chen X, et al (2012). Alpha-fetoprotein acts as a novel signal molecule and mediates transcription of Fn14 in human hepatocellular carcinoma. J Hepatol, 57, 322-9. https://doi.org/10.1016/j.jhep.2012.03.029
  26. Wang S, Zhan M, Yin J, et al (2006). Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis. Oncogene, 25, 3346-56. https://doi.org/10.1038/sj.onc.1209357
  27. Watts GS, Tran NL, Berens ME, et al (2007). Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma. Int J Cancer, 121, 2132-9. https://doi.org/10.1002/ijc.22898
  28. Whitsett TG, Cheng E, Inge L, et al (2012). Elevated expression of Fn14 in non-small cell lung cancer correlates with activated EGFR and promotes tumor cell migration and invasion. Am J Pathol, 181, 111-20. https://doi.org/10.1016/j.ajpath.2012.03.026
  29. Willis AL, Tran NL, Chatigny JM, et al (2008). The fibroblast growth factor-inducible 14 receptor is highly expressed in HER2-positive breast tumors and regulates breast cancer cell invasive capacity. Mol Cancer Res, 6, 725-34. https://doi.org/10.1158/1541-7786.MCR-08-0005
  30. Zhao YM, Wang L, Dai Z, et al (2011). Validity of plasma macrophage migration inhibitory factor for diagnosis and prognosis of hepatocellular carcinoma. Int J Cancer, 129, 2463-72. https://doi.org/10.1002/ijc.25918

Cited by

  1. Elevated PIVKA-II is Associated with Early Recurrence and Poor Prognosis in BCLC 0-A Hepatocellular Carcinomas vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6673
  2. Knockdown of the differentially expressed gene TNFRSF12A inhibits hepatocellular carcinoma cell proliferation and migration in vitro vol.15, pp.3, 2017, https://doi.org/10.3892/mmr.2017.6154
  3. TWEAK/Fn14 signaling in tumors vol.39, pp.6, 2017, https://doi.org/10.1177/1010428317714624