A novel biomarker TERTmRNA is applicable for early detection of hepatoma.
BACKGROUND
We previously reported a highly sensitive method for serum human telomerase reverse transcriptase (hTERT) mRNA for hepatocellular carcinoma (HCC). alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) are good markers for HCC. In this study, we verified the significance of hTERTmRNA in a large scale multi-centered trial, collating quantified values with clinical course.


METHODS
In 638 subjects including 303 patients with HCC, 89 with chronic hepatitis (CH), 45 with liver cirrhosis (LC) and 201 healthy individuals, we quantified serum hTERTmRNA using the real-time RT-PCR. We examined its sensitivity and specificity in HCC diagnosis, clinical significance, ROC curve analysis in comparison with other tumor markers, and its correlations with the clinical parameters using Pearson relative test and multivariate analyses. Furthermore, we performed a prospective and comparative study to observe the change of biomarkers, including hTERTmRNA in HCC patients receiving anti-cancer therapies.


RESULTS
hTERTmRNA was demonstrated to be independently correlated with clinical parameters; tumor size and tumor differentiation (P < 0.001, each). The sensitivity/specificity of hTERTmRNA in HCC diagnosis showed 90.2%/85.4% for hTERT. hTERTmRNA proved to be superior to AFP, AFP-L3, and DCP in the diagnosis and underwent an indisputable change in response to therapy. The detection rate of small HCC by hTERTmRNA was superior to the other markers.


CONCLUSIONS
hTERTmRNA is superior to conventional tumor markers in the diagnosis and recurrence of HCC at an early stage.
Miura
Norimasa
N
Department of Pathophysiological and Therapeutic Science, Tottori University, Japan. mnmiura@hotmail.com
Osaki
Yukio
Y
Nagashima
Miki
M
Kohno
Michimori
M
Yorozu
Kensho
K
Shomori
Kohei
K
Kanbe
Takamasa
T
Oyama
Kenji
K
Kishimoto
Yukihiro
Y
Maruyama
Shigeo
S
Noma
Eijiro
E
Horie
Yutaka
Y
Kudo
Masatoshi
M
Sakaguchi
Seigo
S
Hirooka
Yasuaki
Y
Ito
Hisao
H
Kawasaki
Hironaka
H
Hasegawa
Junichi
J
Shiota
Goshi
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D003937:Diagnosis, Differential; D018450:Disease Progression; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D012372:ROC Curve; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000097:blood / Q000235:genetics*; D055815:Young Adult
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D019098:Telomerase