High intratumoral metastasis-associated in colon cancer-1 expression predicts poor outcomes of cryoablation therapy for advanced hepatocellular carcinoma

Journal of Translational Medicine

Ke-Qin Hu²  Zhen Zeng³  Chun-Ping Wang³  Zhong-Xian Xu³  Lin-Jing An³  Hong Wang³  Zheng Dong³  Wen-Lin Bai³  Yin-Ying Lu³  Xiu-Juan Chang³  Jian-Hui Qu³  Yong-Ping Yang¹ 

[1] Beijing Institute for Infectious Disease, Beijing, China;Division of Gastroenterology/Hepatology, University of California, 101 the City Dr., Building 56, Ste. 237, Irvine, CA 92868, USA;Center of Therapeutic Research for Liver Cancer, the 302nd Hospital, 100 Xi Si Huan Middle Road, Beijing 100039, China

关键词: Outcomes;    Safety;    Efficacy;    Advanced hepatocellular carcinoma;    Metastasis-associated in colon cancer-1 (MACC1);    Cryoablation;   

Others  :  828058
DOI  :  10.1186/1479-5876-11-41

 received in 2012-09-02, accepted in 2013-02-07,  发布年份 2013

【 摘 要 】

Background

Cryoablation is one of the local therapies for hepatocellular carcinoma (HCC), but its safety and effect has not been studied in patients with Child class A or B and Barcelona Clinic Liver Cancer (BCLC) stage C HCC. Metastasis-associated in colon cancer-1 (MACC1) overexpression has been associated with poor prognosis of HCC, but its predictive value to post-cryoablation outcomes remains unknown in patients with BCLC stage C HCC.

Methods

This study assessed the safety and outcomes of cryoablation measured by time to progression (TTP) and overall survival (OS), and predictive value of MACC1 mRNA and protein overexpression in tumorous tissue to post-cryoablation outcomes in 120 advanced HCC patients with child-pugh class A or B by quantitative polymerase chain reaction and immunohistochemical staining. The potenial correlation of MACC1 and c-Met expression to tumor cell proliferation and apoptosis was also analyzed.

Results

The cryoablation in patients with advanced unresectable HCC resulted in a median TTP and OS of 5.5 (4.2- 6.7) months and 10.5 (9.0-12.0) months, respectively and no significant complications, comparable to the historical report for RFA therapy. The MACC1 mRNA and nuclear protein expression was significantly increased in tumorous tissues in these patients than that in normal liver tissue controls. Higher expression of MACC1 mRNA and nuclear protein in tumorous tissues in these patients was associated with shorter post cryoablation median TTP and OS than that with lower MACC1 expression.

Conclusions

Cryoablation is a safe and effective therapeutic option for patients with advanced HCC and Child-pugh class A or B cirrhosis; and a higher intratumoral expression of MACC1 or nuclear translocation predicts poor outcomes of cryotherapy in these patients.

【 授权许可】

   
2013 Yang et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics. CA cancer 2002, 55:74-108.
• [2]Bruix J, Sherman M: Management of hepatocellular carcinoma. Hepatology 2005, 42:1208-1236.
• [3]Park KW, Park JW, Choi JI, Kim TH, Kim SH, Park HS, Lee WJ, Park SJ, Hong EK, Kim CM: Survival analysis of 904 patinets with hepatocellular carcinoma in a hepatitis B virus-endemic area. J Gastroenterol Hepatol 2008, 23:467-473.
• [4]Llovet JM, Fuster J, Bruix J: Barcelona-clinic liver cancer group: The Barcelona approach: Diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl 2004, 10(suppl 1):S115-S120.
• [5]Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A: SHARP Investigators Study Group: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008, 359:378-390.
• [6]Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009, 10:25-34.
• [7]Zuro LM, Staren ED: Cryosurgical ablation of unresectable hepatic tumors. AORN J 1996, 64:231-236. 239–244
• [8]Wong WS, Patel SC, Cruz FS: Cryosurgery as a Treatment for Advanced Stage Hepatocellular Carcinoma. Results, Complications, and Alcohol Ablation. Cancer 1998, 82:1268-1278.
• [9]Osada S, Imai H, Tomita H: Serum cytokine levels in response to hepatic cryoablation. J Surg Oncol 2007, 95:491-498.
• [10]Zhou L, Wang CP, Lu YY, Bai WL, Qu JH, Lou M, Zeng Z, Wu Y, Chen Y, Wang H: Decrease in size of non-treated lesions after cryoablation for hepatocellular carcinoma. Hepatogastroenterology 2012, 59:252-254.
• [11]Zhou L, Fu JL, Lu YY, Fu BY, Wang CP, An LJ, Wang XZ, Zeng Z, Zhou CB, Yang YP: Regulatory T cells are associated with post-cryoablation prognosis in patients with hepatitis B virus-related hepatocellular carcinoma. J Gastroenterol 2010, 45:968-978.
• [12]Chen HW, Lai EC, Zhen ZJ, Cui WZ, Liao S, Lau WY: Ultrasound-guided percutaneous cryotherapy of hepatocellular carcinoma. Int J Surg 2011, 9:188-191.
• [13]Sabel MS: Cryo-immunology: A review of the literature and proposed mechanisms for stimulatory versus suppressive immune responses. Cryobiology 2009, 58:1-11.
• [14]Stein U, Walther W, Arlt F, Schwabe H, Smith J, Fichtner I, Birchmeier W, Schlag PM: MACC1, a newly identified key regulator of HGF/Met signaling, predicts colon cancer metastasis. Nat Med 2009, 15:59-67.
• [15]Shirahata A, Shinmura K, Kitamura Y, Sakuraba K, Yokomizo K, Goto T, Mizukami H, Saito M, Ishibashi K, Kigawa G: MACC1 as a Marker for Advanced Colorectal Carcinoma. Anticancer Res 2010, 30:2689-2692.
• [16]Shirahata A, Sakata M, Kitamura Y, Sakuraba K, Yokomizo K, Goto T, Mizukami H, Saito M, Ishibashi K, Kigawa G: MACC 1 as a Marker for Peritoneal-disseminated Gastric Carcinoma. Anticancer Res 2010, 30:3441-3444.
• [17]Qu JH, Chang XJ, Lu YY, Bai WL, Chen Y, Zhou L, Zeng Z, Wang CP, An LJ, Hao LY: Overexpression of Metastasis-Associated in Colon Cancer-1 Predicts a Poor Outcome of HBV-Related Hepatocellular Carcinoma. World J Gastroenterol 2012, 18:2995-3003.
• [18]Qiu JL, Huang PZ, Liu Q, Hong J, Li BK, Lu CL, Wang L, Wang JP, Yuan YF: Identification of MACC1 as a novel prognostic marker in hepatocellular carcinoma. J Transl Med 2011, 9:166-175. BioMed Central Full Text
• [19]Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009, 45:228-247.
• [20]Lee HS, Kim JK, Cheong JY, Han EJ, An SY, Song JH, Jung YJ, Jeon SC, Jung MW, Jang EJ: Prediction of compensated liver cirrhosis by ultrasonography and routine blood tests in patients with chronic viral hepatitis. Korean J Hepatol 2010, 16:369-375.
• [21]Yamamoto J, Kosuge T, Saiura A, Sakamoto Y, Shimada K, Sano T, Takayama T, Sugawara Y, Yamaguchi T, Kokudo N: Effectiveness of hepatic resection for early-stage hepatocellular carcinoma in cirrhotic patients: subgroup analysis according to Milan Criteria. Jpn J Clin Ocncol 2007, 34:287-295.
• [22]Wang CP, Lu YY, Chen Y, Feng YY, An LJ, Wang XZ, Su SH, Bai WL, Zhou L, Yang YP: Prognostic factors and recurrence of hepatitis B-related hepatocellular carcinoma after argon-helium cryoablation: a prospective study. Clin Exp Metastasis 2009, 26:839-848.
• [23]Bruix J, Hessheimer AJ, Forner A, Boix L, Vilana R, Llovet JM: New aspects of diagnosis and therapy of hepatocellular carcinoma. Oncogene 2006, 25:3848-3856.
• [24]Yang YP, Wang CP, Lu YY, Bai WL, An LJ, Qu JH, Gao XD, Chen Y, Zhou L, Wu Y: Outcomes of ultrasound-guided percutaneous argon-helium cryoablation of hepatocellular carcinoma. J Hepatobiliary Pancreat Sci 2012, 19:674-684.
• [25]Schmittgen TD, Livak KJ: Analyzing real-time PCR data by the comparative C (T) method. Nat Protoc 2008, 3:1101-1108.
• [26]Wang ZL, Liang P, Dong BW, Yu XL, Yu DJ: Prognostic factors and recurrence of small hepatocellular carcinoma after hepatic resection or microwave ablation: a retrospective study. J Gastrointest Surg 2008, 12:327-337.
• [27]Yoo HY, Patt CH, Geschwind JF, Thuluvath PJ: The outcome of liver transplantation in patients with hepatocellular carcinoma in the United States between 1988 and 2001: 5-year survival has improved significantly with time. J Clin Oncol 2003, 21:4329-4335.
• [28]Lopez PM, Villanueva A, Llovet JM: Systematic review: evidence-based management of hepatocellular carcinoma–an updated analysis of randomized controlled trials. Aliment Pharmacol Ther 2006, 23:1535-1547.
• [29]Ng KK, Lam CM, Poon RT, Shek TW, To JY, Wo YH, Ho DW, Fan ST: Comparison of systemic responses of radiofrequency ablation, cryotherapy, and surgical resection in a porcine liver model. Ann Surg Oncol 2004, 11:650-657.
• [30]Machi J, Bueno RS, Wong LL: Long-term follow-up outcome of patients undergoing radiofrequency ablation for unresectable hepatocellular carcinoma. World J Surg 2005, 29:1-10.
• [31]Sala M, Llovet JM, Vilana R, Bianchi L, Solé M, Ayuso C, Brú C, Bruix J, Barcelona Clínic Liver Cancer Group: Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma. Hepatology 2004, 40:1352-1360.
• [32]Raut CP, Izzo F, Marra P, Ellis LM, Vauthey JN, Cremona F, Vallone P, Mastro A, Fornage BD, Curley SA: Significant long-term survival after radiofrequency ablation of unresectable hepatocellular carcinoma in patients with cirrhosis. Ann Surg Oncol 2005, 12:616-628.
• [33]Callstrom MR, Charboneau JW: Technologies for ablation of hepatocellular carcinoma. Gastroenterology 2008, 134:1831-1835.
• [34]Orlacchio A, Bazzocchi G, Pastorelli D, Bolacchi F, Angelico M, Almerighi C, Masala S, Simonetti G: Percutaneous cryoablation of small hepatocellular carcinoma with US guidance and CT monitoring: initial experience. Cardiovasc Intervent Radiol 2008, 31:587-594.
• [35]Shimizu T, Sakuhara Y, Abo D, Hasegawa Y, Kodama Y, Endo H, Shirato H, Miyasaka K: Outcome of MR-guided percutaneous cryoablation for hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 2009, 16:816-823.
• [36]Allaf ME, Varkarakis IM, Bhayani SB, Inagaki T, Kavoussi LR, Solomon SB: Pain control requirements for percutaneous ablation of renal tumors:cryoablation versus radiofrequency ablation–initial observations. Radiology 2005, 237:366-370.
• [37]Wang CP, Wang H, Qu JH, Lu YY, Bai WL, Dong Z, Gao XD, Rong GH, Zeng Z, Yang YP: Tumour seeding after percutaneous cryoablation for hepatocellular carcinoma. World J Gastroenterol 2012, 18:6587-6596.
• [38]Llovet JM, Vilana R, Brú C, Bianchi L, Salmeron JM, Boix L, Ganau S, Sala M, Pagès M, Ayuso C, Barcelona Clínic Liver Cancer (BCLC) Group: Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma. Hepatology 2001, 33:1124-1129.
• [39]Yu J, Liang P, Yu XL, Cheng ZG, Han ZY, Mu MJ, Wang XH: US-guided percutaneous microwave ablation of renal cell carcinoma: intermediate-term results. Eur J Radiol 2012, 263:900-908.
• [40]Kerkar S, Carlin AM, Sohn RL, Steffes C, Tyburski J, Littrup P, Weaver D: Long-term follow up and prognostic factors for cryotherapy of malignant liver tumors. Surgery 2004, 136:770-779.
• [41]Sohn RL, Carlin AM, Steffes C, Tyburski JG, Wilson RF, Littrup PJ, Weaver DW: The extent of cryosurgery increases the complication rate after hepatic cryoablation. Am Surg 2003, 69:317-323.
• [42]Yang Y, Lu Y, Wang C, Bai W, Qu J, Chen Y, Chang X, An L, Zhou L, Zeng Z: Cryotherapy is associated with improved clinical outcomes of sorafenib therapy for advanced hepatocellular carcinoma. Cell Biochem Biophys 2012, 63:159-169.
• [43]Kadouchi K, Higuchi K, Shiba M, Okazaki H, Yamamori K, Sasaki E, Tominaga K, Watanabe T, Fujiwara Y, Oshitani N: What are the risk factors for aggravation of esophageal varices in patients with hepatocellular carcinoma? J Gastroenterol Hepatol 2007, 22:240-246.
• [44]Li Y, Tang ZY, Ye SL, Liu YK, Chen J, Xue Q, Chen J, Gao DM, Bao WH: Establishment of cell clones with different metastatic potential from the metastatic hepatocellularcarcinoma cell line MHCC97. World J Gastroenterol 2001, 7:630-636.
• [45]Shirahata A, Fan W, Sakuraba K, Yokomizo K, Goto T, Mizukami H, Saito M, Ishibashi K, Kigawa G, Nemoto H: MACC 1 as a marker for vascular invasive hepatocellular carcinoma. Anticancer Res 2011, 31:777-780.
• [46]Si MS, Amersi F, Golish SR, Ortiz JA, Zaky J, Finklestein D, Busuttil RW, Imagawa DK: Prevalence of metastases in hepatocellular carcinoma: risk factors and impact on survival. Am Surg 2003, 69:879-885.
• [47]Kang HY, Shin HD, Kim SB, Song IH: Prognosis predictability of hepatocellular carcinoma according to staging systems in hepatitis B virus-endemic area. Clin Res Hepatol Gastroenterol 2012, 36:357-364.
• [48]Tandon P, Garcia-Tsao G: Prognostic indicators in hepatocellular carcinoma: a systematic review of 72 studies. Liver Int 2009, 29:502-508.