Alpha-fetoprotein and human telomerase reverse transcriptase mRNA levels in peripheral blood of patients with hepatocellular carcinoma

  • Sun-Young Kong
  • Joong-Won Park
  • Jin Oak Kim
  • Nam Oak Lee
  • Jung An Lee
  • Kyung Woo Park
  • Eun Kyung Hong
  • Chang-Min Kim
Original Paper

Abstract

Purpose

Tumor-associated gene expression in peripheral blood reflects the presence of circulating hepatocellular carcinoma (HCC) cells and might be associated with aggressive features of HCC. We assessed the prognostic significance of alpha-fetoprotein (AFP) and human telomerase reverse transcriptase protein (hTERT) mRNA expression in the peripheral blood of HCC patients.

Methods

About 343 HCC patients, treated at the National Cancer Center, Korea, were included in this study. We measured AFP and hTERT mRNA levels in peripheral blood using quantitative real-time reverse transcription polymerase chain reaction. The association between the expression of each gene and survival was analyzed.

Results

AFP and hTERT mRNA were detected in 204 (59.5%) and 48 (14.0%) patients with HCC, respectively. The mean AFP copy number was 203 copies/μL (range 0–19992 copies/μL) and that of hTERT was 26 copies/μL (0–1711 copies/μL). AFP mRNA expression was correlated with the number of tumors (P = 0.05), but there were no significant association between hTERT expression and clinical features. There was also no relationship between overall survival and AFP (P = 0.08) or hTERT (P = 0.67) mRNA expression.

Conclusions

This is the first report to evaluate the association between peripheral blood hTERT mRNA expression, and survival of HCC patients. The results indicate that AFP and hTERT mRNA expression in peripheral blood may not be useful HCC prognostic markers.

Keywords

Alpha-fetoprotein (AFP) Human telomerase reverse transcriptase (hTERT) Circulating tumor cells Hepatocellular carcinoma (HCC) Survival Prognosis 

References

  1. Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42:1208–1236. doi:10.1002/hep.20933 PubMedCrossRefGoogle Scholar
  2. Cillo U, Navaglia F, Vitale A, Molari A, Basso D, Bassanello M, Brolese A, Zanus G, Montin U, D’Amico F, Ciarleglio FA, Carraro A, Bridda A, Burra P, Carraro P, Plebani M, D’Amico DF (2004) Clinical significance of alpha-fetoprotein mRNA in blood of patients with hepatocellular carcinoma. Clin Chim Acta 347:129–138. doi:10.1016/j.cccn.2004.04.032 PubMedCrossRefGoogle Scholar
  3. El-Serag HB, Siegel AB, Davila JA, Shaib YH, Cayton-Woody M, McBride R, McGlynn KA (2006) Treatment and outcomes of treating of hepatocellular carcinoma among medicare recipients in the United States: a population-based study. J Hepatol 44:158–166. doi:10.1016/j.jhep.2005.10.002 PubMedCrossRefGoogle Scholar
  4. Funaki N, Tanaka J, Seto S, Kasamatsu T, Kaido T, Imamura M (1995) Highly-sensitive identification of alpha-fetoprotein mRNA in circulating peripheral blood of hepatocellular carcinoma patients. Life Sci 57:1621–1631. doi:10.1016/0024-3205(95)02138-9 PubMedCrossRefGoogle Scholar
  5. Funaki NO, Tanaka J, Seto SI, Kasamatsu T, Kaido T, Imamura M (1997) Hematogenous spreading of hepatocellular carcinoma cells: possible participation in recurrence in the liver. Hepatology 25:564–568. doi:10.1002/hep.510250312 PubMedCrossRefGoogle Scholar
  6. Gross-Goupil M, Saffroy R, Azoulay D, Precetti S, Emile JF, Delvart V, Tindiliere F, Laurent A, Bellin MF, Bismuth H, Debuire B, Lemoine A (2003) Real-time quantification of AFP mRNA to assess hematogenous dissemination after transarterial chemoembolization of hepatocellular carcinoma. Ann Surg 238:241–248PubMedGoogle Scholar
  7. Lechel A, Manns MP, Rudolph KL (2004) Telomeres and telomerase: new targets for the treatment of liver cirrhosis and hepatocellular carcinoma. J Hepatol 41:491–497. doi:10.1016/j.jhep.2004.06.010 PubMedCrossRefGoogle Scholar
  8. Lemoine A, Le Bricon T, Salvucci M, Azoulay D, Pham P, Raccuia J, Bismuth H, Debuire B (1997) Prospective evaluation of circulating hepatocytes by alpha-fetoprotein mRNA in humans during liver surgery. Ann Surg 226:43–50. doi:10.1097/00000658-199707000-00006 PubMedCrossRefGoogle Scholar
  9. Louha M, Poussin K, Ganne N, Zylberberg H, Nalpas B, Nicolet J, Capron F, Soubrane O, Vons C, Pol S, Beaugrand M, Berthelot P, Franco D, Trinchet JC, Brechot C, Paterlini P (1997) Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer. Hepatology 26:998–1005. doi:10.1002/hep.510260430 PubMedCrossRefGoogle Scholar
  10. Miura N, Shiota G, Nakagawa T, Maeda Y, Sano A, Marumoto A, Kishimoto Y, Murawaki Y, Hasegawa J (2003) Sensitive detection of human telomerase reverse transcriptase mRNA in the serum of patients with hepatocellular carcinoma. Oncology 64:430–434. doi:10.1159/000070303 PubMedCrossRefGoogle Scholar
  11. Miura N, Maeda Y, Kanbe T, Yazama H, Takeda Y, Sato R, Tsukamoto T, Sato E, Marumoto A, Harada T, Sano A, Kishimoto Y, Hirooka Y, Murawaki Y, Hasegawa J, Shiota G (2005) Serum human telomerase reverse transcriptase messenger RNA as a novel tumor marker for hepatocellular carcinoma. Clin Cancer Res 11:3205–3209. doi:10.1158/1078-0432.CCR-04-1487 PubMedCrossRefGoogle Scholar
  12. Mozdy AD, Cech TR (2006) Low abundance of telomerase in yeast: implications for telomerase haploinsufficiency. RNA 12:1721–1737. doi:10.1261/rna.134706 PubMedCrossRefGoogle Scholar
  13. Park J (2004) Practice guideline for diagnosis and treatment of hepatocellular carcinoma. Korean J Hepatol 10:88–98PubMedGoogle Scholar
  14. Park KW, Park JW, Choi JI, Kim TH, Kim SH, Park HS, Lee WJ, Park SJ, Hong EK, Kim CM (2008) Survival analysis of 904 patients with hepatocellular carcinoma in a hepatitis B virus-endemic area. J Gastroenterol Hepatol 23:467–473. doi:10.1111/j.1440-1746.2007.05112.x PubMedCrossRefGoogle Scholar
  15. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMedCrossRefGoogle Scholar
  16. Sato S, Noguchi Y, Wada H, Fujita S, Nakamura S, Tanaka R, Nakada T, Hasegawa K, Nakagawa K, Koizumi F, Ono T, Nouso K, Jungbluth A, Chen YT, Old LJ, Shiratori Y, Nakayama E (2005) Quantitative real-time RT-PCR analysis of NY-ESO-1 and LAGE-1a mRNA expression in normal tissues and tumors, and correlation of the protein expression with the mRNA copy number. Int J Oncol 26:57–63PubMedGoogle Scholar
  17. Tung-Ping Poon R, Fan ST, Wong J (2000) Risk factors, prevention, and management of postoperative recurrence after resection of hepatocellular carcinoma. Ann Surg 232:10–24. doi:10.1097/00000658-200007000-00003 PubMedCrossRefGoogle Scholar
  18. Ueno S, Tanabe G, Nuruki K, Hamanoue M, Komorizono Y, Oketani M, Hokotate H, Inoue H, Baba Y, Imamura Y, Aikou T (2002) Prognostic performance of the new classification of primary liver cancer of Japan (4th ed) for patients with hepatocellular carcinoma: a validation analysis. Hepatol Res 24:395–403. doi:10.1016/S1386-6346(02)00144-4 PubMedCrossRefGoogle Scholar
  19. Waguri N, Suda T, Nomoto M, Kawai H, Mita Y, Kuroiwa T, Igarashi M, Kobayashi M, Fukuhara Y, Aoyagi Y (2003) Sensitive and specific detection of circulating cancer cells in patients with hepatocellular carcinoma; detection of human telomerase reverse transcriptase messenger RNA after immunomagnetic separation. Clin Cancer Res 9:3004–3011PubMedGoogle Scholar
  20. Witzigmann H, Geissler F, Benedix F, Thiery J, Uhlmann D, Tannapfel A, Wittekind C, Hauss J (2002) Prospective evaluation of circulating hepatocytes by alpha-fetoprotein messenger RNA in patients with hepatocellular carcinoma. Surgery 131:34–43. doi:10.1067/msy.2002.118954 PubMedCrossRefGoogle Scholar
  21. Wong IH, Yeo W, Leung T, Lau WY, Johnson PJ (2001) Circulating tumor cell mRNAs in peripheral blood from hepato cellular carcinoma patients under radiotherapy, surgical resection or chemotherapy: a quantitative evaluation. Cancer Lett 167:183–191. doi:10.1016/S0304-3835(01)00455-4 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sun-Young Kong
    • 1
  • Joong-Won Park
    • 2
  • Jin Oak Kim
    • 2
  • Nam Oak Lee
    • 2
  • Jung An Lee
    • 2
  • Kyung Woo Park
    • 3
  • Eun Kyung Hong
    • 2
  • Chang-Min Kim
    • 2
  1. 1.Center for Clinical Services, Department of Laboratory MedicineResearch Institute and Hospital, National Cancer CenterGoyangRepublic of Korea
  2. 2.Center for Liver Cancer, Research Institute and HospitalNational Cancer CenterGoyangRepublic of Korea
  3. 3.Center for Cancer Prevention and Detection, Research Institute and HospitalNational Cancer CenterGoyangRepublic of Korea

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