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Published in: Medical Oncology 3/2012

01-09-2012 | Original Paper

miR-203 expression predicts outcome after liver transplantation for hepatocellular carcinoma in cirrhotic liver

Authors: Hong-Yuan Chen, Zhong-Bo Han, Jun-Wei Fan, Jun Xia, Jun-Yi Wu, Guo-Qiang Qiu, Hua-Mei Tang, Zhi-Hai Peng

Published in: Medical Oncology | Issue 3/2012

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Abstract

Many recent studies have shown the utility of microRNAs (miRs) as cancer-related biomarkers. The aim of the present study was to evaluate the correlation between miR-203 expression and prognosis of patients with hepatocellular carcinoma (HCC) and cirrhosis after liver transplantation (LT). Sixty-six HCC samples from patients who had undergone LT were examined for miR-203 expression using quantitative reverse transcription–polymerase chain reaction. The data were correlated with clinicopathological parameters and prognosis. Patient survival was analyzed by the Kaplan–Meier method and log-rank test. Cox regression was used for multivariate analysis of prognostic factors. We found that miR-203 expression was low in tumor tissues of patients (n = 16) with post-LT HCC recurrence in comparison with those in patients with non-recurrence (n = 50) (P = 0.003). Patients with higher miR-203 expression had significantly better recurrence-free survival (RFS) and overall survival (OS) (P = 0.016 for RFS; P = 0.014 for OS). Multivariate analysis revealed that high-miR-203 expression was an independent predictor of good prognosis (HR 0.202, P = 0.006 for RFS; HR 0.332, P = 0.013 for OS). Our results suggest that miR-203 could be a novel prognostic marker in HCC patients who have undergone LT and might also be a potential therapeutic target.
Literature
1.
go back to reference El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76.PubMedCrossRef El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76.PubMedCrossRef
2.
go back to reference Botha JF, Langnas AN. Liver transplantation for hepatocellular carcinoma: an update. J Natl Compr Canc Netw. 2006;4(8):762–7.PubMed Botha JF, Langnas AN. Liver transplantation for hepatocellular carcinoma: an update. J Natl Compr Canc Netw. 2006;4(8):762–7.PubMed
3.
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.PubMedCrossRef
4.
5.
go back to reference 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. N Engl J Med. 1996;334(11):693–9.PubMedCrossRef 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. N Engl J Med. 1996;334(11):693–9.PubMedCrossRef
6.
go back to reference Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.PubMedCrossRef Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.PubMedCrossRef
7.
go back to reference Zimmerman MA, Ghobrial RM, Tong MJ, Hiatt JR, Cameron AM, Hong J, et al. Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg. 2008;143(2):182–8.PubMedCrossRef Zimmerman MA, Ghobrial RM, Tong MJ, Hiatt JR, Cameron AM, Hong J, et al. Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators. Arch Surg. 2008;143(2):182–8.PubMedCrossRef
8.
go back to reference Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10(1):35–43.PubMedCrossRef Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10(1):35–43.PubMedCrossRef
9.
10.
go back to reference Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, et al. A MicroRNA targeting dicer for metastasis control. Cell. 2010;141(7):1195–207.PubMedCrossRef Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, et al. A MicroRNA targeting dicer for metastasis control. Cell. 2010;141(7):1195–207.PubMedCrossRef
11.
12.
13.
go back to reference Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 2008;13(1):48–57.PubMedCrossRef Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 2008;13(1):48–57.PubMedCrossRef
14.
go back to reference Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, et al. miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol. 2004;1(2):106–13.PubMedCrossRef Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, et al. miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol. 2004;1(2):106–13.PubMedCrossRef
15.
go back to reference Tsai WC, Hsu PWC, Lai TC, Chau GY, Lin CW, Chen CM, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49(5):1571–82.PubMedCrossRef Tsai WC, Hsu PWC, Lai TC, Chau GY, Lin CW, Chen CM, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49(5):1571–82.PubMedCrossRef
16.
go back to reference Group ALTS. A randomized prospective multi-institutional trial of orthotopic liver transplantation or partial hepatic resection with or without adjuvant chemotherapy for hepatocellular carcinoma. Investigators Booklet and Protocol. 1998. Group ALTS. A randomized prospective multi-institutional trial of orthotopic liver transplantation or partial hepatic resection with or without adjuvant chemotherapy for hepatocellular carcinoma. Investigators Booklet and Protocol. 1998.
17.
go back to reference Edmondson HA, Steiner PE. Primary carcinoma of the liver. a study of 100 cases among 48,900 necropsies. Cancer. 1954;7(3):462–503.PubMedCrossRef Edmondson HA, Steiner PE. Primary carcinoma of the liver. a study of 100 cases among 48,900 necropsies. Cancer. 1954;7(3):462–503.PubMedCrossRef
18.
go back to reference Li X, Zhang Y, Ding J, Wu K, Fan D. Survival prediction of gastric cancer by a seven-microRNA signature. Gut. 2009;59(5):579–85.PubMedCrossRef Li X, Zhang Y, Ding J, Wu K, Fan D. Survival prediction of gastric cancer by a seven-microRNA signature. Gut. 2009;59(5):579–85.PubMedCrossRef
19.
go back to reference Cherqui D, Laurent A, Mocellin N, Tayar C, Luciani A, Van Nhieu JT, et al. Liver resection for transplantable hepatocellular carcinoma: long-term survival and role of secondary liver transplantation. Ann Surg. 2009;250(5):738–46.PubMedCrossRef Cherqui D, Laurent A, Mocellin N, Tayar C, Luciani A, Van Nhieu JT, et al. Liver resection for transplantable hepatocellular carcinoma: long-term survival and role of secondary liver transplantation. Ann Surg. 2009;250(5):738–46.PubMedCrossRef
20.
21.
go back to reference Vibert E, Azoulay D, Hoti E, Iacopinelli S, Samuel D, Salloum C, et al. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant. 2010;10(1):129–37.PubMedCrossRef Vibert E, Azoulay D, Hoti E, Iacopinelli S, Samuel D, Salloum C, et al. Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant. 2010;10(1):129–37.PubMedCrossRef
22.
go back to reference Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.PubMedCrossRef Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.PubMedCrossRef
23.
go back to reference Jonas S, Bechstein WO, Steinm¨¹ller T, Herrmann M, Radke C, Berg T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33(5):1080–6.PubMedCrossRef Jonas S, Bechstein WO, Steinm¨¹ller T, Herrmann M, Radke C, Berg T, et al. Vascular invasion and histopathologic grading determine outcome after liver transplantation for hepatocellular carcinoma in cirrhosis. Hepatology. 2001;33(5):1080–6.PubMedCrossRef
26.
27.
go back to reference Zhang J, Yang Y, Yang T, Liu Y, Li A, Fu S, et al. microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity. Br J Cancer. 2010;103:1215–20.PubMedCrossRef Zhang J, Yang Y, Yang T, Liu Y, Li A, Fu S, et al. microRNA-22, downregulated in hepatocellular carcinoma and correlated with prognosis, suppresses cell proliferation and tumourigenicity. Br J Cancer. 2010;103:1215–20.PubMedCrossRef
28.
go back to reference Wong CCL, Wong CM, Tung EKK, Au SLK, Lee JMF, Poon RTP, et al. The micoRNA MiR-139 suppresses metastasis and progression of hepatocellular carcinoma by downregulating Rho-kinase 2 (ROCK2). Gastroenterology. 2011;140(1):322–31.PubMedCrossRef Wong CCL, Wong CM, Tung EKK, Au SLK, Lee JMF, Poon RTP, et al. The micoRNA MiR-139 suppresses metastasis and progression of hepatocellular carcinoma by downregulating Rho-kinase 2 (ROCK2). Gastroenterology. 2011;140(1):322–31.PubMedCrossRef
29.
go back to reference Furuta M, Kozaki K, Tanaka S, Arii S, Imoto I, Inazawa J. miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis. 2010;31(5):766–76.PubMedCrossRef Furuta M, Kozaki K, Tanaka S, Arii S, Imoto I, Inazawa J. miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis. 2010;31(5):766–76.PubMedCrossRef
30.
go back to reference Bueno MJ, et al. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008;13(6):496–506.PubMedCrossRef Bueno MJ, et al. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell. 2008;13(6):496–506.PubMedCrossRef
31.
go back to reference Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299(4):425–36.PubMedCrossRef Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299(4):425–36.PubMedCrossRef
32.
go back to reference Ikenaga N, Ohuchida K, Mizumoto K, Yu J, Kayashima T, Sakai H, et al. MicroRNA-203 expression as a new Prognostic marker of pancreatic adenocarcinoma. Ann Surg Oncol. 2010;17:3120–8.PubMedCrossRef Ikenaga N, Ohuchida K, Mizumoto K, Yu J, Kayashima T, Sakai H, et al. MicroRNA-203 expression as a new Prognostic marker of pancreatic adenocarcinoma. Ann Surg Oncol. 2010;17:3120–8.PubMedCrossRef
33.
go back to reference Greither T, Grochola LF, Udelnow A, Lautenschl ger C, et al. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer. 2010;126(1):73–80.PubMedCrossRef Greither T, Grochola LF, Udelnow A, Lautenschl ger C, et al. Elevated expression of microRNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer. 2010;126(1):73–80.PubMedCrossRef
34.
go back to reference Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.PubMedCrossRef Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.PubMedCrossRef
35.
go back to reference Schlitt HJ, Neipp M, Weimann A, Oldhafer KJ, Schmoll E, Boeker K, et al. Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation. J Clin Oncol. 1999;17(1):324–31.PubMed Schlitt HJ, Neipp M, Weimann A, Oldhafer KJ, Schmoll E, Boeker K, et al. Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation. J Clin Oncol. 1999;17(1):324–31.PubMed
36.
37.
go back to reference Viticchie G, Lena AM, Latina A, Formosa A, Gregersen LH, Lund AH et al. MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell cycle (Georgetown, Tex). 2011;10(7):1–11. Viticchie G, Lena AM, Latina A, Formosa A, Gregersen LH, Lund AH et al. MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell cycle (Georgetown, Tex). 2011;10(7):1–11.
38.
go back to reference Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol. 2009;11(12):1487–95.PubMedCrossRef Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A, et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol. 2009;11(12):1487–95.PubMedCrossRef
39.
go back to reference Huang J, Qiu Y, Chen G, Huang L, He J. The relationship between Bmi-1 and the epithelial–mesenchymal transition in lung squamous cell carcinoma. Medical Oncol. 2011. doi:10.1007/s12032-011-9998-5. Huang J, Qiu Y, Chen G, Huang L, He J. The relationship between Bmi-1 and the epithelial–mesenchymal transition in lung squamous cell carcinoma. Medical Oncol. 2011. doi:10.​1007/​s12032-011-9998-5.
Metadata
Title
miR-203 expression predicts outcome after liver transplantation for hepatocellular carcinoma in cirrhotic liver
Authors
Hong-Yuan Chen
Zhong-Bo Han
Jun-Wei Fan
Jun Xia
Jun-Yi Wu
Guo-Qiang Qiu
Hua-Mei Tang
Zhi-Hai Peng
Publication date
01-09-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-0031-9

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