Down-regulation of retinol binding protein 5 is associated with aggressive tumor features in hepatocellular carcinoma
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Acyclic retinoid (ACR) has been shown to be a promising chemopreventive agent for hepatocellular carcinoma (HCC) after curative resection. The effects of retinoid are mediated by retinol-binding proteins (RBPs) through regulating cell proliferation and differentiation.
Patients and methods
This study investigated the clinical significance of RBP5 in HCC. RBP5 mRNA level was examined by real-time quantitative PCR on 52 matched tumor and adjacent non-tumor liver tissues, and on ten normal livers. Expression of RBP5 protein was examined using Western blotting analysis and immunohistochemistry.
Down-regulation of RBP5 was found in HCC tissues at both mRNA and protein levels. Decreased RBP5 level was closely related to poor differentiation (P = 0.02) and large tumor size (P = 0.01). Low level of RPB5 was associated with poor overall survival (P = 0.02), and was an independent prognostic factor for HCC.
Our study revealed that RBP5 down-regulation in HCC was associated with aggressive tumor features, suggesting an important role of RPB5 in HCC progression.
KeywordsCellular retinol binding protein Prognosis
This study was supported in part by the grants from the Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery, and Seed Funding Program of the University of Hong Kong.
- Ades L, Chevret S, De Botton S, Thomas X, Dombret H, Beve B, Sanz M, Guerci A, Miguel JS, Dela Serna J, Garo C, Stoppa AM, Reman O, Stamatoulas A, Fey M, Cahn JY, Sotto JJ, Bourhis JH, Parry A, Chomienne C, Degos L, Fenaux P (2005) Outcome of acute promyelocytic leukemia treated with all trans retinoic acid and chemotherapy in elderly patients: the European group experience. Leukemia 19:230–233PubMedCrossRefGoogle Scholar
- Brabender J, Metzger R, Salonga D, Danenberg KD, Danenberg PV, Holscher AH, Schneider PM (2005) Comprehensive expression analysis of retinoic acid receptors and retinoid X receptors in non-small cell lung cancer: implications for tumor development and prognosis. Carcinogenesis 26:525–530PubMedCrossRefGoogle Scholar
- Kurie JM, Lotan R, Lee JJ, Lee JS, Morice RC, Liu DD, Xu XC, Khuri FR, Ro JY, Hittelman WN, Walsh GL, Roth JA, Minna JD, Hong WK (2003) Treatment of former smokers with 9-cis-retinoic acid reverses loss of retinoic acid receptor-beta expression in the bronchial epithelium: results from a randomized placebo-controlled trial. J Natl Cancer Inst 95:206–214PubMedCrossRefGoogle Scholar
- Muto Y, Moriwaki H, Ninomiya M, Adachi S, Saito A, Takasaki KT, Tanaka T, Tsurumi K, Okuno M, Tomita E, Nakamura T, Kojima T (1996) Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group. N Engl J Med 334:1561–1567PubMedCrossRefGoogle Scholar
- Schmitt-Graff A, Ertelt V, Allgaier HP, Koelble K, Olschewski M, Nitschke R, Bochaton-Piallat ML, Gabbiani G, Blum HE (2003) Cellular retinol-binding protein-1 in hepatocellular carcinoma correlates with beta-catenin, Ki-67 index, and patient survival. Hepatology 38:470–480PubMedCrossRefGoogle Scholar
- Sobin LH, Whitekind C (1997) TNM classification of malignant tumours, 5th edn. Wiley, New YorkGoogle Scholar
- Takai K, Okuno M, Yasuda I, Matsushima-Nishiwaki R, Uematsu T, Tsurumi H, Shiratori Y, Muto Y, Moriwaki H (2005) Prevention of second primary tumors by an acyclic retinoid in patients with hepatocellular carcinoma. Updated analysis of the long-term follow-up data. Intervirology 48:39–45PubMedCrossRefGoogle Scholar
- Yasuda I, Shiratori Y, Adachi S, Obora A, Takemura M, Okuno M, Shidoji Y, Seishima M, Muto Y, Moriwaki H (2002) Acyclic retinoid induces partial differentiation, down-regulates telomerase reverse transcriptase mRNA expression and telomerase activity, and induces apoptosis in human hepatoma-derived cell lines. J Hepatol 36:660–667PubMedCrossRefGoogle Scholar