Sensitive Detection of Human Telomerase Reverse Transcriptase mRNA in the Serum of Patients with Hepatocellular Carcinoma

Miura, Naruhisa; Shiota, Goshi; Nakagawa, Terumichi; Maeda, Yoshiko; Sano, Akiko; Marumoto, Akira; Kishimoto, Yukihiro; Murawaki, Yoshikazu; Hasegawa, Junichi

doi:10.1159/000070303

Cited by 62 publications

(68 citation statements)

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“…Centrifugation of collected blood and harvesting serum samples were done by using three steps of centrifugation (800 Â g with 0.45 Am filtration, 1,000 Â g, and 1,500 Â g) to decrease lymphocyte to a minimum as previously described (9). To confirm the effective removal of lymphocytes which are contained in serum, CD2, CD3, CD8, CD19, CD22, and CD68 expressions were examined by using h2-microglobin as an expression control.…”

Section: Methodsmentioning

confidence: 99%

“…Second, other conventional tumor markers such as a-fetoprotein (AFP) and des-g-carboxy prothrombin (DCP) are widely used in clinical scenes of HCC. In our previous study, we reported that the sensitive method for detecting tumor-derived hTERT mRNA in serum was superior to AFP level for the early detection of HCC patients whose AFP levels were low (9). In the present study, by newly developed quantified detection system of serum hTERT, we mainly focused on the comparison of hTERT mRNA with AFP mRNA, AFP, and DCP for HCC diagnosis because AFP mRNA is the most sensitive marker of the known markers for HCC, and show for the first time that measurement of hTERT mRNA is superior to the conventional tumor markers, such as AFP, DCP, and AFP mRNA, in HCC diagnosis.…”

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confidence: 99%

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

Miura¹,

Maeda²,

Kanbe³

et al. 2005

Clinical Cancer Research

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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 a-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-g-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.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Miura¹,

Maeda²,

Kanbe³

et al. 2005

Clinical Cancer Research

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“…Furthermore, it has also been demonstrated to be a novel and available marker for HCC diagnosis. The expression of hTERT mRNA in the serum of HCC patients is significantly higher than that in the serum of healthy adults or patients with nonmalignant hepatopathy [50,51] , and the use of newly developed real-time quantitative reverse transcription polymerase chain reaction may improve the effectiveness of determination [50] . It has been reported that the sensitivity and specificity of hTERT mRNA in detecting HCC are 88.2% and 70.0%, respectively, which excel those of conventional tumor markers, such as AFP mRNA, AFP and DCP [50] .…”

Section: Genesmentioning

confidence: 99%

“…It has been reported that the sensitivity and specificity of hTERT mRNA in detecting HCC are 88.2% and 70.0%, respectively, which excel those of conventional tumor markers, such as AFP mRNA, AFP and DCP [50] . Moreover, it has been indicated that the expression of serum hTERT mRNA, which is associated with the serum concentration of AFP, tumor size, and tumor differentiation degree (P < 0.001, each), may be a valuable indicator of poor prognosis for HCC patients [50,51] . There are some other markers in this category, which could be used as diagnostic or prognostic indicators for HCC.…”

Section: Genesmentioning

confidence: 99%

Serum tumor markers for detection of hepatocellular carcinoma

Zhou¹

2006

WJG

311

259

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Alpha-fetoprotein and alpha-fetoprotein-L3Alpha fetoprotein (AFP) is a fetal specific glycoprotein produced primarily by the fetal liver. Normally, its serum concentration falls rapidly after birth and its synthesis in adult life is repressed. However, greater than 70% of HCC patients have a high serum concentration of AFP because of the tumor excretion. Forty years after its discovery, serum AFP remains a most useful tumor marker in screening HCC patients. The serum concentration of 20 ng/mL is the most commonly used cut-off value to differentiate HCC patients from healthy adults in clinical researches. However, some investigations have showed that the cut-off value is fluctuant in different ethnic groups. REVIEW Serum tumor markers for detection of hepatocellular carcinoma AbstractHepatocellular carcinoma (HCC) is one of the most frequent malignant tumors and is the second most common cause of cancer death in China. Therefore, it is very important to detect this disease and the recurrence at its earlier period. Serum tumor markers, as the effective method for detecting hepatocellular carcinoma for a long time, could be divided into 4 categories: oncofetal antigens and glycoprotein antigens; enzymes and isoenzymes; genes; and cytokines. Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting patients with hepatocellular carcinoma, and has been proven to have capability of prefiguring the prognosis. However, it has been indicated that AFP-L3 and DCP excel AFP in differentiating hepatocellular c a r c i n o m a f r o m n o n m a l i g n a n t h e p a t o p a t h y a n d detecting small hepatocellular carcinoma. Some tumor markers, such as human cervical cancer oncogene and human telomerase reverse transcriptase mRNA, have also been indicated to have higher accuracies than AFP. Furthermore, some other tumor markers, such as glypican-3, gamma-glutamyl transferase II, alpha-lfucosidase, transforming growth factor-beta1, tumorspecific growth factor, have been indicated to be available supplementaries to AFP in the detection. AFP mRNA has been shown to correlate with the metastasis and recurrence of HCC, and it may be the most useful marker to prefigure the prognosis. Some other markers, such as gamma-glutamyl transferase mRNA, vascular endothelial growth factor, and interleukin-8, could also be used as available prognostic indicators, and the simultaneous determination of AFP and these markers may detect the recurrence of HCC at its earlier period.

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“…During the last ten years, there has been a great leap forward in detecting and testing isolated cell-free RNA for different tumourrelated transcripts [38,39], telomerase components [40] or viral RNA transcripts. Tumour-associated RNA was shown to be detectable in the serum or plasma of patients with breast, liver and lung cancer [41], colorectal cancer [42], follicular lymphoma [43], prostate cancer [44], malignant melanoma [45], hepatocelular carcinoma [46], oesophagel carcinoma, and head and neck squamous cell carcinoma [47]. A very limited number of studies have attempted to investigate the feasibility of identifying mRNAs that are potentially predictive of the response to therapy.…”

Section: Cancer Diagnosticsmentioning

confidence: 99%

Circulating nucleic acids as a new diagnostic tool

Urbanová

Plzák²,

Strnad

et al. 2010

Cellular and Molecular Biology Letters

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The discovery of circulating nucleic acids in the 1940s opened up new possibilities for the non-invasive detection, monitoring and screening of various human disorders. Several tumour markers that enable early cancer detection or tumour behaviour prediction have been detected in the plasma of cancer patients. Maternal plasma analysis can be used to detect certain fetal abnormalities, with the quantification of cell-free nucleic acids used to screen for several pregnancy-associated disorders. Some other applications are in transplant monitoring and graft rejection assessment, and in certain medical emergencies such as trauma and burn severity stratification. Many studies have yielded promising results in this field, but the techniques have yet to be applied in routine clinical practice. Large-scale studies using similar technologies and a broad spectrum of patients are still needed to verify the results of the various studies.

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Sensitive Detection of Human Telomerase Reverse Transcriptase mRNA in the Serum of Patients with Hepatocellular Carcinoma

Cited by 62 publications

References 12 publications

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

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

Serum tumor markers for detection of hepatocellular carcinoma

Circulating nucleic acids as a new diagnostic tool

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