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Serum Human Telomerase Reverse Transcriptase Messenger RNA as a Novel Tumor Marker for Hepatocellular Carcinoma

Authors' Affiliations: ¹ Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, ² Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, ³ Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, ⁴ Division of Surgery and Clinical Medicine, Department of Surgery, Tottori University School of Medicine; and ⁵ Internal Medicine, San-in Labor Welfare Hospital, Yonago, Japan

Requests for reprints: Norimasa Miura, Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Tottori University Schol of Medicine, 86 Nishicho, Yonago, Tottori 683-8503, Japan. Phone: 81-859-34-8014; Fax: 81-859-34-8140; E-mail: mnmiura{at}grape.med.tottori-u.ac.jp.

Purpose: We previously reported the usefulness of a qualified highly sensitive detection method for human telomerase reverse transcriptase (hTERT) mRNA in serum with 89.7% sensitivity for hepatocellular carcinoma (HCC). In this study, we developed a quantitative detection method for serum hTERT mRNA and examined the clinical significance in HCC diagnosis.

Experimental Background: In 64 patients with HCC, 20 with liver cirrhosis, 20 with chronic hepatitis, and 50 healthy individuals, we measured serum hTERT mRNA by using the newly developed real-time quantitative reverse transcription-PCR with SYBR Green I. We examined its sensitivity and specificity in HCC diagnosis, clinical significance in comparison with other tumor markers, and its correlations with the clinical variables by using multivariate analyses.

Results: Serum hTERT mRNA showed higher values in patients with HCC than those with chronic liver diseases. hTERT mRNA expression was shown to be independently correlated with clinical variables such as tumor size, number, and degree of differentiation (P < 0.001, each). The sensitivity/specificity of hTERT mRNA and alpha;-fetoprotein (AFP) mRNA in HCC diagnosis were 88.2%/70.0% for hTERT and 71.6%/67.5% for AFP, respectively. hTERT mRNA proved to be superior to AFP mRNA, AFP, and des--carboxy prothrombin in HCC diagnosis. Furthermore, hTERT mRNA in serum was associated with that in HCC tissue.

Conclusions: The usefulness of hTERT mRNA expression in HCC diagnosis and its superiority to conventional tumor markers were shown. Therefore, serum hTERT mRNA is a novel and available marker for HCC diagnosis.

Key Words: hTERT • real-time RT-PCR • cancer diagnosis • hepatocellular carcinoma • tumor marker

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