Advertisement

Metastasis of Hepatic Cancer

  • Zhaoyou Tang

Abstract

Hepatic cancer, mostly hepatocellular carcinoma (HCC), ranked third in the world in terms of cancer mortality, and 55% of HCC deaths were in China. Intrahepatic and extrahepatic metastasis in the lung, bone and lymph node are common in symptomatic patients, being the major cause of HCC death. The incidence rate of extrahepatic metastasis reported after medical treatment of HCC, was approximately 13% at 5 years; presence of viral markers, large tumor, multiple tumor nodules, vascular invasion and elevated tumor markers were risk factors. After treatment, the recurrent rate was high. The 5-year recurrent rate was 61.5% after curative HCC resection, and 43.5% after small HCC resection. The recurrent rate was even higher in patients receiving ablation therapies. In a study of hepatitis B virus (HBV)-DNA integration, we demonstrated that both a unicentric and a multicentric origin existed in recurrent lesions. It is accepted that most of the early recurrence came from the primary tumor in the nature of metastasis (unicentric origin), whereas most of the late recurrence (3 years after treatment) might be of multicentric origin. With the aid of laboratory findings and medical imaging, diagnosis is not difficult. Surgery remains the treatment choice for solitary and small metastatic lesion in the liver and some extrahepatic metastases. Loco-regional ablation is an alternative surgery. Radiotherapy is a choice for some patients with lymph node, bone, portal vein (PV) or inferior vena cava (IVC) involvement. Sorafenib may be a choice for advanced patients.

Keywords

Hepatocellular Carcinoma Clin Oncol Inferior Vena Cava Human Hepatocellular Carcinoma Tumor Thrombus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    Parkin D M, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin, 2005, 55: 74–108.PubMedCrossRefGoogle Scholar
  2. [2]
    Kanda M, Tateishi R, Yoshida H, et al. Extrahepatic metastasis of hepatocellular carcinoma: incidence and risk factors. Liver Int, 2008, 28: 1256–1263.PubMedCrossRefGoogle Scholar
  3. [3]
    Tang Z Y. Small hepatocellular carcinoma. In: Tang Z Y, Wu M C, Xia S S (eds). Primary Liver Cancer. Berlin: Springer-Verlag, 1989: 191–203.Google Scholar
  4. [4]
    Liang X H, Loncarevic I F, Tang Z Y, et al. Resection of hepatocellular carcinoma: oligocentric origin of recurrent and multinodular tumours. J Gastroenterol Hepatol, 1991, 6: 77–80.PubMedCrossRefGoogle Scholar
  5. [5]
    Tang Z Y, Ye S L, Liu Y K, et al. A decade’s studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol, 2004, 130: 187–196.PubMedCrossRefGoogle Scholar
  6. [6]
    Budhu A, Forgues M, Ye Q H, et al. Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell, 2006, 10: 99–111.PubMedCrossRefGoogle Scholar
  7. [7]
    Gao Q, Qiu S J, Fan J, et al. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. Journal of Clinical Oncology, 2007, 25: 2586–2593.PubMedCrossRefGoogle Scholar
  8. [8]
    Zhu X D, Zhang J B, Zhuang P Y, et al. High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol, 2008, 26: 2707–2716.PubMedCrossRefGoogle Scholar
  9. [9]
    Ye Q H, Qin L X, Forgues M, et al. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med, 2003, 9: 416–423.PubMedCrossRefGoogle Scholar
  10. [10]
    Ding S J, Li Y, Tan Y X, et al. From proteomic analysis to clinical significance: overexpression of cytokeratin 19 correlates with hepatocellular carcinoma metastasis. Mol Cell Proteomics, 2004, 3: 73–81.PubMedGoogle Scholar
  11. [11]
    Zhang T, Sun H C, Xu Y, et al. Overexpression of platelet-derived growth factor receptor alpha in endothelial cells of hepatocellular carcinoma associated with high metastatic potential. Clin Cancer Res, 2005, 11: 8557–8563.PubMedCrossRefGoogle Scholar
  12. [12]
    Qin L X, Tang Z Y, Sham J S, et al. The association of chromosome 8p deletion and tumor metastasis in human hepatocellular carcinoma. Cancer Res, 1999, 59: 5662–5665.PubMedGoogle Scholar
  13. [13]
    Yang G H, Fan J, Xu Y, et al. Osteopontin combined with CD44, a novel prognostic biomarker for patients with hepatocellular carcinoma undergoing curative resection. Oncologist, 2008, 13: 1155–1165.PubMedCrossRefGoogle Scholar
  14. [14]
    Yang X R, Xu Y, Shi G M, et al. Cytokeratin 10 and cytokeratin 19: predictive markers for poor prognosis in hepatocellular carcinoma patients after curative resection. Clin Cancer Res, 2008, 14: 3850–3859.PubMedCrossRefGoogle Scholar
  15. [15]
    Li Y, Tian B, Yang J, et al. Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics. J Cancer Res Clin Oncol, 2004, 130: 460–468.PubMedCrossRefGoogle Scholar
  16. [16]
    Ji X N, Ye S L, Li Y, et al. Contributions of lung tissue extracts to invasion and migration of human hepatocellular carcinoma cells with various metastatic potentials. J Cancer Res Clin Oncol, 2003, 129: 556–564.PubMedCrossRefGoogle Scholar
  17. [17]
    Huang X Y, Wang L, Huang Z L, et al. Herbal extract “Songyou Yin” inhibits tumor growth and prolongs survival in nude mice bearing human hepatocellular carcinoma xenograft with high metastatic potential. J Cancer Res Clin Oncol, 2009, 135: 1245–1255.PubMedCrossRefGoogle Scholar
  18. [18]
    Ju M J, Qiu S J, Fan J, et al. Peritumoral activated hepatic stellate cells predict poor clinical outcome in hepatocellular carcinoma after curative resection. Am J Clin Pathol, 2009, 131: 498–510.PubMedCrossRefGoogle Scholar
  19. [19]
    Ou D P, Tao Y M, Tang F Q, et al. The hepatitis B virus X protein promotes hepatocellular carcinoma metastasis by upregulation of matrix metalloproteinases. Int J Cancer, 2007, 120: 1208–1214.PubMedCrossRefGoogle Scholar
  20. [20]
    Sun H C, Zhang W, Qin L X, et al. Positive serum hepatitis B e antigen is associated with higher risk of early recurrence and poorer survival in patients after curative resection of hepatitis B-related hepatocellular carcinoma. Journal of Hepatology, 2007, 47: 684–690.PubMedCrossRefGoogle Scholar
  21. [21]
    Zhou X D, Yu Y Q, Tang Z Y, et al. Surgical treatment of recurrent hepatocellular carcinoma. Hepatogastroenterology, 1993, 40: 333–336.PubMedGoogle Scholar
  22. [22]
    Wang J, Li Q, Sun Y, et al. Clinicopathologic features between multicentric occurence and intrahepatic metastasis of multiple hepatocellular carcinomas related to HBV. Surg Oncol, 2009, 18: 25–30.PubMedCrossRefGoogle Scholar
  23. [23]
    He J, Zeng Z C, Tang Z Y, et al. Clinical features and prognostic factors in patients with bone metastases from hepatocellular carcinoma receiving external beam radiotherapy. Cancer, 2009, 115: 2710–2720.PubMedCrossRefGoogle Scholar
  24. [24]
    Kim S U, Kim do Y, Park J Y, et al. Hepatocellular carcinoma presenting with bone metastasis: clinical characteristics and prognostic factors. J Cancer Res Clin Oncol, 2008, 134: 1377–1384.PubMedCrossRefGoogle Scholar
  25. [25]
    Chang S S, Luo J C, Chao Y, et al. The clinical features and prognostic factors of hepatocellular carcinoma patients with spinal metastasis. Eur J Gastroenterol Hepatol, 2001, 13: 1341–1345.PubMedCrossRefGoogle Scholar
  26. [26]
    Shibata T, Maetani Y, Ametani F, et al. Percutaneous ethanol injection for treatment of adrenal metastasis from hepatocellular carcinoma. AJR Am J Roentgenol, 2000, 174: 333–335.PubMedGoogle Scholar
  27. [27]
    Hsieh M J, Lu CH, Tsai N W, et al. Prediction, clinical characteristics and prognosis of intracerebral hemorrhage in hepatocellular carcinoma patients with intracerebral metastasis. J Clin Neurosci, 2009, 16: 394–398.PubMedCrossRefGoogle Scholar
  28. [28]
    Choi H J, Cho B C, Sohn J H, et al. Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC. J Neurooncol, 2009, 91: 307–313.PubMedCrossRefGoogle Scholar
  29. [29]
    Chang L, Chen Y L, Kao M C. Intracranial metastasis of hepatocellular carcinoma: review of 45 cases. Surg Neurol, 2004, 62: 172–177.PubMedCrossRefGoogle Scholar
  30. [30]
    Sun H C, Zhuang P Y, Qin L X, et al. Incidence and prognostic values of lymph node metastasis in operable hepatocellular carcinoma and evaluation of routine complete lymphadenectomy. J Surg Oncol, 2007, 96: 37–45.PubMedCrossRefGoogle Scholar
  31. [31]
    Ju M J, Qiu S J, Fan J, et al. Preoperative serum gamma-glutamyl transferase to alanine aminotransferase ratio is a convenient prognostic marker for Child-Pugh A hepatocellular carcinoma after operation. J Gastroenterol, 2009, 44: 635–642.CrossRefGoogle Scholar
  32. [32]
    Wilson S R, Burns P N, Muradali D, et al. Harmonic hepatic US with microbubble contrast agent: initial experience showing improved characterization of hemangioma, hepatocellular carcinoma, and metastasis. Radiology, 2000, 215: 153–161.PubMedGoogle Scholar
  33. [33]
    Yoon K T, Kim J K, Kim do Y, et al. Role of 18F-fluorodeoxyglucose positron emission tomography in detecting extrahepatic metastasis in pretreatment staging of hepatocellular carcinoma. Oncology, 2007, 72 Suppl 1: 104–110.PubMedCrossRefGoogle Scholar
  34. [34]
    Sueyoshi K, Narabayashi I, Doi K, et al. Tc-99m PMT whole-body scintigraphy for evaluated of therapeutic effect and for monitoring bone metastasis in a patient with hepatocellular carcinoma. Clin Nucl Med, 2000, 25: 1000–1003.PubMedCrossRefGoogle Scholar
  35. [35]
    Tang Z Y, Yu Y Q, Zhou X D. An important approach to prolonging survival further after radical resection of AFP positive hepatocellular carcinoma. J Exp Clin Cancer Res, 1984, 3: 359–366.Google Scholar
  36. [36]
    Sun H C, Tang Z Y, Ma Z C, et al. The prognostic factor for outcome following second resection for intrahepatic recurrence of hepatocellular carcinoma with a hepatitis B virus infection background. J Cancer Res Clin Oncol, 2005, 131: 284–288.PubMedCrossRefGoogle Scholar
  37. [37]
    Zhou X D, Tang Z Y, Yu Y Q, et al. Long-term survivors after resection for primary liver cancer. Clinical analysis of 19 patients surviving more than ten years. Cancer, 1989, 63: 2201–2206.PubMedCrossRefGoogle Scholar
  38. [38]
    Nakajima J, Tanaka M, Matsumoto J, et al. Appraisal of surgical treatment for pulmonary metastasis from hepatocellular carcinoma. World J Surg, 2005, 29: 715–718.PubMedCrossRefGoogle Scholar
  39. [39]
    Koide N, Kondo H, Suzuki K, et al. Surgical treatment of pulmonary metastasis from hepatocellular carcinoma. Hepatogastroenterology, 2007, 54: 152–156.PubMedGoogle Scholar
  40. [40]
    Tomimaru Y, Sasaki Y, Yamada T, et al. The significance of surgical resection for pulmonary metastasis from hepatocellular carcinoma. Am J Surg, 2006, 192: 46–51.PubMedCrossRefGoogle Scholar
  41. [41]
    Park J S, Yoon D S, Kim K S, et al. What is the best treatment modality for adrenal metastasis from hepatocellular carcinoma? J Surg Oncol, 2007, 96: 32–36.PubMedCrossRefGoogle Scholar
  42. [42]
    Lin C P, Cheng J S, Lai K H, et al. Gastrointestinal metastasis in hepatocellular carcinoma: radiological and endoscopic studies of 11 cases. J Gastroenterol Hepatol, 2000, 15: 536–541.PubMedCrossRefGoogle Scholar
  43. [43]
    Zeng Z C, Tang Z Y, Fan J, et al. Consideration of role of radiotherapy for lymph node metastases in patients with HCC: retrospective analysis for prognostic factors from 125 patients. Int J Radiat Oncol Biol Phys, 2005, 63: 1067–1076.PubMedCrossRefGoogle Scholar
  44. [44]
    Park Y J, Lim do H, Paik S W, et al. Radiation therapy for abdominal lymph node metastasis from hepatocellular carcinoma. J Gastroenterol, 2006, 41: 1099–1106.PubMedCrossRefGoogle Scholar
  45. [45]
    Zeng Z C, Tang Z Y, Fan J, et al. Radiation therapy for adrenal gland metastases from hepatocellular carcinoma. Jpn J Clin Oncol, 2005, 35: 61–67.PubMedCrossRefGoogle Scholar
  46. [46]
    Zeng Z C, Fan J, Tang Z Y, et al. A comparison of treatment combinations with and without radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombus. Int J Radiat Oncol Biol Phys, 2005, 61: 432–443.PubMedCrossRefGoogle Scholar
  47. [47]
    Zeng Z C, Fan J, Tang Z Y, et al. Prognostic factors for patients with hepatocellular carcinoma with macroscopic portal vein or inferior vena cava tumor thrombi receiving external-beam radiation therapy. Cancer Sci, 2008, 99: 2510–2517.PubMedCrossRefGoogle Scholar
  48. [48]
    Huang Y J, Tung W C, Hsu H C, et al. Radiation therapy to non-iatrogenic subcutaneous metastasis in hepatocellular carcinoma: results of a case series. Br J Radiol, 2008, 81: 143–150.PubMedCrossRefGoogle Scholar
  49. [49]
    Jiang W, Zeng Z C, Tang Z Y, et al. Benefit of radiotherapy for 90 patients with resected intrahepatic cholangiocarcinoma and concurrent lymph node metastases. J Cancer Res Clin Oncol, 2010, 136: 1323–1331.PubMedCrossRefGoogle Scholar
  50. [50]
    Hosogi H, Ikai I, Hatano E, et al. Complete response by a combination of 5-fluorouracil and interferon-alpha chemotherapy for lung metastasis of hepatocellular carcinoma after hepatic resection with portal and hepatic vein tumor thrombectomy. Hepatol Res, 2005, 33: 320–324.PubMedCrossRefGoogle Scholar
  51. [51]
    Rashidi B, An Z, Sun F X, et al. Efficacy of intra-hepatectomy 5-Fu on recurrence and metastasis of human hepatocellular carcinoma in nude mice. Int J Cancer, 2001, 91: 231–235.PubMedCrossRefGoogle Scholar
  52. [52]
    Chung Y H, Song I H, Song B C, et al. Combined therapy consisting of intraarterial cisplatin infusion and systemic interferon-alpha for hepatocellular carcinoma patients with major portal vein thrombosis or distant metastasis. Cancer, 2000, 88: 1986–1991.PubMedCrossRefGoogle Scholar
  53. [53]
    Llovet J M, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 2008, 359: 378–390.PubMedCrossRefGoogle Scholar
  54. [54]
    Yau T, Chan P, Ng K K, et al. Phase 2 open-label study of single-agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B-endemic Asian population: presence of lung metastasis predicts poor response. Cancer, 2009, 115: 428–436.PubMedCrossRefGoogle Scholar
  55. [55]
    Wang Z, Zhou J, Fan J, et al. Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma. Clin Cancer Res, 2008, 14: 5124–5130.PubMedCrossRefGoogle Scholar
  56. [56]
    Li X M, Tang Z Y, Zhou G, et al. Significance of vascular endothelial growth factor mRNA expression in invasion and metastasis of hepatocellular carcinoma. J Exp Clin Cancer Res, 1998, 17: 13–17.PubMedGoogle Scholar
  57. [57]
    Zheng X Y, Ling Z Y, Tang Z Y, et al. The abundance of NM23-H1 mRNA is related with in situ microenvironment and intrahepatic metastasis in hepato-cellular carcinoma. J Exp Clin Cancer Res, 1998, 17: 337–341.PubMedGoogle Scholar
  58. [58]
    Sun H C, Tang Z Y, Zhou G, et al. KAI1 gene expression in hepatocellular carcinoma and its relationship with intrahepatic metastases. J Exp Clin Cancer Res, 1998, 17: 307–311.PubMedGoogle Scholar
  59. [59]
    Qin L X, Tang Z Y, Ye S L, et al. Chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma when high and low metastatic models are compared. J Cancer Res Clin Oncol, 2001, 127: 482–488.PubMedCrossRefGoogle Scholar
  60. [60]
    Zhang L H, Qin L X, Ma Z C, et al. Allelic imbalance regions on chromosomes 8p, 17p and 19p related to metastasis of hepatocellular carcinoma: comparison between matched primary and metastatic lesions in 22 patients by genome-wide microsatellite analysis. J Cancer Res Clin Oncol, 2003, 129: 279–286.PubMedGoogle Scholar
  61. [61]
    Yang J, Qin L X, Ye S L, et al. The abnormalities of chromosome 8 in two hepatocellular carcinoma cell clones with the same genetic background and different metastatic potential. J Cancer Res Clin Oncol, 2003, 129: 303–308.PubMedGoogle Scholar
  62. [62]
    Wu X, Jia H L, Wang Y F, et al. HTPAP gene on chromosome 8p is a candidate metastasis suppressor for human hepatocellular carcinoma. Oncogene, 2006, 25: 1832–1840.PubMedCrossRefGoogle Scholar
  63. [63]
    Lei K F, Wang Y F, Zhu X Q, et al. Identification of MSRA gene on chromosome 8p as a candidate metastasis suppressor for human hepatitis B virus-positive hepatocellular carcinoma. Bmc Cancer, 2007, 7: 172.PubMedCrossRefGoogle Scholar
  64. [64]
    Zhao L, Qin L X, Ye Q H, et al. KIAA0008 gene is associated with invasive phenotype of human hepatocellular carcinoma: a functional analysis. J Cancer Res Clin Oncol, 2004, 130: 719–727.PubMedCrossRefGoogle Scholar
  65. [65]
    Zhou J, Tang Z Y, Fan J, et al. Expression of platelet-derived endothelial cell growth factor and vascular endothelial growth factor in hepatocellular carcinoma and portal vein tumor thrombus. J Cancer Res Clin Oncol, 2000, 126: 57–61.PubMedCrossRefGoogle Scholar
  66. [66]
    Zheng Q, Tang Z Y, Xue Q, et al. Invasion and metastasis of hepatocellular carcinoma in relation to urokinase-type plasminogen activator, its receptor and inhibitor. J Cancer Res Clin Oncol, 2000, 126: 641–646.PubMedCrossRefGoogle Scholar
  67. [67]
    Cui J F, Liu Y K, Pan B S, et al. Differential proteomic analysis of human hepatocellular carcinoma cell line metastasis-associated proteins. J Cancer Res Clin Oncol, 2004, 130: 615–622.PubMedCrossRefGoogle Scholar
  68. [68]
    Song H Y, Liu Y K, Feng J T, et al. Proteomic analysis on metastasisassociated proteins of human hepatocellular carcinoma tissues. J Cancer Res Clin Oncol, 2006, 132: 92–98.PubMedCrossRefGoogle Scholar
  69. [69]
    Shen H, Cheng G, Fan H, et al. Expressed proteome analysis of human hepatocellular carcinoma in nude mice (LCI-D20) with high metastasis potential. Proteomics, 2006, 6: 528–537.PubMedCrossRefGoogle Scholar
  70. [70]
    Cui J F, Liu Y K, Zhang L J, et al. Identification of metastasis candidate proteins among HCC cell lines by comparative proteome and biological function analysis of S100A4 in metastasis in vitro. Proteomics, 2006, 6: 5953–5961.PubMedCrossRefGoogle Scholar
  71. [71]
    Jia W D, Sun H C, Zhang J B, et al. A novel peptide that selectively binds highly metastatic hepatocellular carcinoma cell surface is related to invasion and metastasis. Cancer Lett, 2007, 247: 234–242.PubMedCrossRefGoogle Scholar
  72. [72]
    Dai Z, Liu Y K, Cui J F, et al. Identification and analysis of altered alpha1,6-fucosylated glycoproteins associated with hepatocellular carcinoma metastasis. Proteomics, 2006, 6: 5857–5867.PubMedCrossRefGoogle Scholar
  73. [73]
    Budhu A, Jia H L, Forgues M, et al. Identification of metastasis-related microRNAs in hepatocellular carcinoma. Hepatology, 2008, 47: 897–907.PubMedCrossRefGoogle Scholar
  74. [74]
    Tian B, Li Y, Ji X N, et al. Basement membrane proteins play an active role in the invasive process of human hepatocellular carcinoma cells with high metastasis potential. J Cancer Res Clin Oncol, 2005, 131: 80–86.PubMedCrossRefGoogle Scholar
  75. [75]
    Qin L X, Tang Z Y. Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature. J Cancer Res Clin Oncol, 2004, 130: 497–513.PubMedCrossRefGoogle Scholar
  76. [76]
    Ju M J, Qiu S J, Gao Q, et al. Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma. Cancer Sci, 2009, 100: 1267–1274.PubMedCrossRefGoogle Scholar
  77. [77]
    Li X M, Tang Z Y, Qin L X, et al. Serum vascular endothelial growth factor is a predictor of invasion and metastasis in hepatocellular carcinoma. J Exp Clin Cancer Res, 1999, 18: 511–517.PubMedGoogle Scholar
  78. [78]
    Sun J J, Zhou X D, Liu Y K, et al. Invasion and metastasis of liver cancer: expression of intercellular adhesion molecule 1. J Cancer Res Clin Oncol, 1999, 125: 28–34.PubMedCrossRefGoogle Scholar
  79. [79]
    Zhou J, Tang Z Y, Fan J, et al. The potential of plasma thrombomodulin as a biomarker of portal vein tumor thrombus in hepatocellular carcinoma. J Cancer Res Clin Oncol, 2001, 127: 559–564.PubMedCrossRefGoogle Scholar
  80. [80]
    Zhang H, Ye Q H, Ren N, et al. The prognostic significance of preoperative plasma levels of osteopontin in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol, 2006, 132: 709–717.PubMedCrossRefGoogle Scholar
  81. [81]
    Li Y, Tang Z Y, Tian B, et al. Serum CYFRA 21-1 level reflects hepatocellular carcinoma metastasis: study in nude mice model and clinical patients. J Cancer Res Clin Oncol, 2006, 132: 515–520.PubMedCrossRefGoogle Scholar
  82. [82]
    Niu Q, Tang Z Y, Qin L X, et al. Loss of heterozygosity at D14S62 and D14S51 detected by a simple and non-radioactive method in plasma DNA is a potential marker of metastasis and recurrence after curative hepatic resection in hepatocellular carcinoma. Hepatogastroenterology, 2003, 50: 1579–1582.PubMedGoogle Scholar
  83. [83]
    Ren N, Qin L X, Tu H, et al. The prognostic value of circulating plasma DNA level and its allelic imbalance on chromosome 8p in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol, 2006, 132: 399–407.PubMedCrossRefGoogle Scholar
  84. [84]
    Pang J Z, Qin L X, Ren N, et al. Loss of heterozygosity at D8S298 is a predictor for long-term survival of patients with tumor-node-metastasis stage I of hepatocellular carcinoma. Clin Cancer Res, 2007, 13: 7363–7369.PubMedCrossRefGoogle Scholar
  85. [85]
    Pan H W, Ou Y H, Peng S Y, et al. Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma. Cancer, 2003, 98: 119–127.PubMedCrossRefGoogle Scholar
  86. [86]
    Jia J B, Zhuang P Y, Sun H C, et al. Protein expression profiling of vascular endothelial growth factor and its receptors identifies subclasses of hepatocellular carcinoma and predicts survival. J Cancer Res Clin Oncol, 2009, 135: 847–854.PubMedCrossRefGoogle Scholar
  87. [87]
    Bai D S, Dai Z, Zhou J, et al. Capn4 overexpression underlies tumor invasion and metastasis after liver transplantation for hepatocellular carcinoma. Hepatology, 2009, 49: 460–470.PubMedCrossRefGoogle Scholar
  88. [88]
    Zhuang P Y, Zhang J B, Zhu X D, et al. Two pathologic types of hepatocellular carcinoma with lymph node metastasis with distinct prognosis on the basis of CK19 expression in tumor. Cancer, 2008, 112: 2740–2748.PubMedCrossRefGoogle Scholar
  89. [89]
    Yamashita T, Forgues M, Wang W, et al. EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. Cancer Res, 2008, 68: 1451–1461.PubMedCrossRefGoogle Scholar
  90. [90]
    Hoshida Y, Villanueva A, Kobayashi M, et al. Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med, 2008, 359: 1995–2004.PubMedCrossRefGoogle Scholar
  91. [91]
    Sun H C, Tang Z Y. Preventive treatments for recurrence after curative resection of hepatocellular carcinoma: a literature review of randomized control trials. World J Gastroenterol, 2003, 9: 635–640.PubMedGoogle Scholar
  92. [92]
    Wang L, Tang Z Y, Qin L X, et al. High-dose and long-term therapy with interferon-alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. Hepatology, 2000, 32: 43–48.PubMedCrossRefGoogle Scholar
  93. [93]
    Sun H C, Tang Z Y, Wang L, et al. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-related hepatocellular carcinoma: a randomized clinical trial. J Cancer Res Clin Oncol, 2006, 132: 458–465.PubMedCrossRefGoogle Scholar
  94. [94]
    Wang L, Wu W Z, Sun H C, et al. Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice. J Gastrointest Surg, 2003, 7: 587–594.PubMedCrossRefGoogle Scholar
  95. [95]
    Wu W Z, Sun H C, Shen Y F, et al. Interferon alpha 2a down-regulates VEGF expression through PI3 kinase and MAP kinase signaling pathways. J Cancer Res Clin Oncol, 2005, 131: 169–178.PubMedCrossRefGoogle Scholar
  96. [96]
    Wu W Z, Sun H C, Gao Y Q, et al. Reduction in p48-ISGFgamma levels confers resistance to interferon-alpha2a in MHCC97 cells. Oncology, 2004, 67: 428–440.PubMedCrossRefGoogle Scholar
  97. [97]
    Qian Y B, Zhang J B, Wu W Z, et al. P48 is a predictive marker for outcome of postoperative interferon-alpha treatment in patients with hepatitis B virus infection-related hepatocellular carcinoma. Cancer, 2006, 107: 1562–1529.PubMedCrossRefGoogle Scholar
  98. [98]
    Ji J, Shi J, Budhu A, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med, 2009, 361: 1437–1447.PubMedCrossRefGoogle Scholar
  99. [99]
    Ren Z G, Lin Z Y, Xia J L, et al. Postoperative adjuvant arterial chemoembolization improves survival of hepatocellular carcinoma patients with risk factors for residual tumor: a retrospective control study. World J Gastroenterol, 2004, 10: 2791–2794.PubMedGoogle Scholar
  100. [100]
    Xia J L, Yang B H, Tang Z Y, et al. Inhibitory effect of the angiogenesis inhibitor TNP-470 on tumor growth and metastasis in nude mice bearing human hepatocellular carcinoma. J Cancer Res Clin Oncol, 1997, 123: 383–387.PubMedGoogle Scholar
  101. [101]
    Bu W, Tang Z Y, Sun F X, et al. Effects of matrix metalloproteinase inhibitor BB-94 on liver cancer growth and metastasis in a patient-like orthotopic model LCI-D20. Hepatogastroenterology, 1998, 45: 1056–1061.PubMedGoogle Scholar
  102. [102]
    Liao Y, Tang Z Y, Ye S L, et al. Modulation of apoptosis, tumorigenesity and metastatic potential with antisense H-Ras oligodeoxynucleotides in a high metastatic tumor model of hepatoma: LCI-D20. Hepatogastroenterology, 2000, 47: 365–370.PubMedGoogle Scholar
  103. [103]
    Sun J J, Zhou X D, Liu Y K, et al. Inhibitory effects of synthetic beta peptide on invasion and metastasis of liver cancer. J Cancer Res Clin Oncol, 2000, 126: 595–600.PubMedCrossRefGoogle Scholar
  104. [104]
    Zhou J, Tang Z Y, Fan J, et al. Capecitabine inhibits postoperative recurrence and metastasis after liver cancer resection in nude mice with relation to the expression of platelet-derived endothelial cell growth factor. Clin Cancer Res, 2003, 9: 6030–6037.PubMedGoogle Scholar
  105. [105]
    Xiao Y S, Tang Z Y, Fan J, et al. Interferon-alpha 2a up-regulated thymidine phosphorylase and enhanced antitumor effect of capecitabine on hepatocellular carcinoma in nude mice. J Cancer Res Clin Oncol, 2004, 130: 546–550.PubMedCrossRefGoogle Scholar
  106. [106]
    Li W C, Ye S L, Sun R X, et al. Inhibition of growth and metastasis of human hepatocellular carcinoma by antisense oligonucleotide targeting signal transducer and activator of transcription 3. Clin Cancer Res, 2006, 12: 7140–7148.PubMedCrossRefGoogle Scholar
  107. [107]
    Li P C, Li Y, Tang Z Y, et al. Study on the inhibitory effect of tyroserleutide on tumor growth and metastasis in nude mice model of human hepatocellular carcinoma metastasis. Hepatogastroenterology, 2007, 54: 1359–1363.PubMedGoogle Scholar
  108. [108]
    Sun B S, Dong Q Z, Ye Q H, et al. Lentiviral-mediated miRNA against osteopontin suppresses tumor growth and metastasis of human hepatocellular carcinoma. Hepatology, 2008, 48: 1834–1842.PubMedCrossRefGoogle Scholar
  109. [109]
    Wang W, Wu F, Fang F, et al. Inhibition of invasion and metastasis of hepatocellular carcinoma cells via targeting RhoC in vitro and in vivo. Clin Cancer Res, 2008, 14: 6804–6812.PubMedCrossRefGoogle Scholar
  110. [110]
    Wang Z, Zhou J, Fan J, et al. Sirolimus inhibits the growth and metastatic progression of hepatocellular carcinoma. J Cancer Res Clin Oncol, 2009, 135: 715–722.PubMedCrossRefGoogle Scholar
  111. [111]
    Zhao J, Dong L, Lu B, et al. Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis. Gastroenterology, 2008, 135: 956–968.PubMedCrossRefGoogle Scholar
  112. [112]
    Taras D, Blanc J F, Rullier A, et al. Pravastatin reduces lung metastasis of rat hepatocellular carcinoma via a coordinated decrease of MMP expression and activity. J Hepatol, 2007, 46: 69–76.PubMedCrossRefGoogle Scholar
  113. [113]
    Lau S H, Sham J S, Xie D, et al. Clusterin plays an important role in hepatocellular carcinoma metastasis. Oncogene, 2006, 25: 1242–1250.PubMedCrossRefGoogle Scholar
  114. [114]
    Lu X, Qin W, Li J, et al. The growth and metastasis of human hepatocellular carcinoma xenografts are inhibited by small interfering RNA targeting to the subunit ATP6L of proton pump. Cancer Res, 2005, 65: 6843–6849.PubMedCrossRefGoogle Scholar
  115. [115]
    Lewis B C, Klimstra D S, Socci N D, et al. The absence of p53 promotes metastasis in a novel somatic mouse model for hepatocellular carcinoma. Mol Cell Biol, 2005, 25: 1228–1237.PubMedCrossRefGoogle Scholar
  116. [116]
    Boissan M, Wendum D, Arnaud-Dabernat S, et al. Increased lung metastasis in transgenic NM23-Null/SV40 mice with hepatocellular carcinoma. J Natl Cancer Inst, 2005, 97: 836–845.PubMedCrossRefGoogle Scholar
  117. [117]
    Lee T K, Poon R T, Yuen A P, et al. Rac activation is associated with hepatocellular carcinoma metastasis by up-regulation of vascular endothelial growth factor expression. Clin Cancer Res, 2006, 12: 5082–5089.PubMedCrossRefGoogle Scholar
  118. [118]
    Lee T K, Poon R T, Yuen A P, et al. Twist overexpression correlates with hepatocellular carcinoma metastasis through induction of epithelialmesenchymal transition. Clin Cancer Res, 2006, 12: 5369–5376.PubMedCrossRefGoogle Scholar
  119. [119]
    Lee T K, Man K, Ho J W, et al. FTY720: a promising agent for treatment of metastatic hepatocellular carcinoma. Clin Cancer Res, 2005, 11: 8458–8466.PubMedCrossRefGoogle Scholar
  120. [120]
    Sun F X, Tang Z Y, Lui K D, et al. Establishment of a metastatic model of human hepatocellular carcinoma in nude mice via orthotopic implantation of histologically intact tissues. Int J Cancer, 1996, 66: 239–243.PubMedCrossRefGoogle Scholar
  121. [121]
    Shao D M, Wang Q H, Chen C, et al. N-acetylglucosaminyltransferase V activity in metastatic models of human hepatocellular carcinoma in nude mice. J Exp Clin Cancer Res, 1999, 18: 331–335.PubMedGoogle Scholar
  122. [122]
    Sun H C, Li X M, Xue Q, et al. Study of angiogenesis induced by metastatic and non-metastatic liver cancer by corneal micropocket model in nude mice. World J Gastroenterol, 1999, 5: 116–118.PubMedGoogle Scholar
  123. [123]
    Tian J, Tang Z Y, Ye S L, et al. New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis. Br J Cancer, 1999, 81: 814–821.PubMedCrossRefGoogle Scholar
  124. [124]
    Li Y, Tang Z Y, Ye S L, et al. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97. World J Gastroenterol, 2001, 7: 630–636.PubMedGoogle Scholar
  125. [125]
    Li Y, Tang Y, Ye L, et al. Establishment of a hepatocellular carcinoma cell line with unique metastatic characteristics through in vivo selection and screening for metastasis-related genes through cDNA microarray. J Cancer Res Clin Oncol, 2003, 129: 43–51.PubMedCrossRefGoogle Scholar
  126. [126]
    Xu Y, Sun H C, Tian B, et al. Establishment of green fluorescent protein-expressing hepatocellular carcinoma cell lines with different metastatic potential: relevant models for in vivo monitoring of metastasis and angiogenesis. J Cancer Res Clin Oncol, 2004, 130: 375–382.PubMedCrossRefGoogle Scholar
  127. [127]
    Yang B W, Liang Y, Xia J L, et al. Biological characteristics of fluorescent protein-expressing human hepatocellular carcinoma xenograft model in nude mice. Eur J Gastroenterol Hepatol, 2008, 20: 1077–1084.PubMedCrossRefGoogle Scholar
  128. [128]
    Yamauchi K, Yang M, Hayashi K, et al. Induction of cancer metastasis by cyclophosphamide pretreatment of host mice: an opposite effect of chemotherapy. Cancer Res, 2008, 68: 516–520.PubMedCrossRefGoogle Scholar
  129. [129]
    Hayden E C. Cutting off cancer’s supply lines. Nature, 2009, 458: 686–687.PubMedCrossRefGoogle Scholar
  130. [130]
    Liu L, Ren Z G, Shen Y, et al. Influence of hepatic artery occlusion on tumor growth and metastatic potential in a human orthotopic hepatoma nude mouse model: relevance of epithelial-mesenchymal transition. Cancer Sci, 2010, 101: 120–128.PubMedCrossRefGoogle Scholar
  131. [131]
    Xiong W, Ren Z G, Qiu S J, et al. Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin. Bmc Cancer, 2010, 10: 219.PubMedCrossRefGoogle Scholar
  132. [132]
    Liu L, Zhu X D, Wang W Q, et al. Activation of beta-catenin by hypoxia in hepatocellular carcinoma contributes to enhanced metastatic potential and poor prognosis. Clin Cancer Res, 2010, 16: 2740–2750.PubMedCrossRefGoogle Scholar
  133. [133]
    Zhang W, Zhu X D, Sun H C, et al. Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects. Clin Cancer Res, 2010, 16: 3420–3430.PubMedCrossRefGoogle Scholar

Copyright information

© Zhejiang University Press, Hangzhou and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Zhaoyou Tang
    • 1
    • 2
  1. 1.Ministry of EducationKey Laboratory of Carcinogenesis and Cancer Invasion of Fudan UniversityShanghaiChina
  2. 2.Liver Cancer Institute and Zhongshan Hospital of Fudan UniversityShanghaiChina

Personalised recommendations