No abstract

Using a newly developed assay of telomerase reverse transcriptase (hTERT) mRNA in serum by real-time RT-PCR, we previously reported this assay to be superior to other tumor markers for hepatoma. In this study, we aimed to clarify its clinical significance as a biomarker for lung cancer. In 112 patients with lung tumor and 80 individuals without cancer, we measured serum hTERT mRNA and epidermal growth factor receptor (EGFR) mRNA levels, using a quantitative one-step real-time RT-PCR assay. We examined its sensitivity and specificity in lung cancer diagnosis, its clinical significance in comparison with other tumor markers, and its correlation with the clinical parameters using multivariate analyses and correlation relative tests. The copy number of serum hTERT mRNA was independently correlated with tumor size, tumor number, presence of metastasis and recurrence, and smoking (all P < 0.05). EGFR mRNA correlated with tumor number and clinical stage (both P < 0.05). The sensitivity and specificity in lung cancer diagnosis were 89.0% and 72.7% for hTERT mRNA, and 71.3% and 80.0% for EGFR mRNA, respectively. hTERT mRNA was superior to other tumor markers in lung cancer diagnosis. For both mRNAs, serum levels were significantly correlated with levels in lung cancer tissues (both P < 0.05). The copy number of hTERT mRNA significantly decreased after the surgical treatment. The data suggest that hTERT mRNA, especially when combined with EGFR mRNA, is a novel and excellent biomarker for pulmonary malignancies to diagnose and assess the clinical stage. (Cancer Sci 2006; 97: 1366-1373) L ung cancer is the leading cause of malignancy-related mortality (1) with little change in the survival rates over the past two decades.(2) NSCLC now accounts for about three-quarters of all cases of lung cancer (3) and most patients continue to die of progressive metastatic disease despite the development of new therapeutic strategies and advances in surgical treatment. Serum tumor markers are non-invasive diagnostic tools for malignant tumors and they are commonly used for the screening of cancer and as an indicator of the treatment effect. In SCLC, neuronspecific enolase and pro-gastrin-releasing peptide are effective markers. In NSCLC, CEA, SCCA, and CYFRA 21-1 are commonly used for screening, and at least one marker among CEA, SCCA and CYFRA is positive in approximately 70% of patients with NSCLC.(4) According to the histological category, the positive rates of CEA and CYFRA are high in patients with ADC, and the positive rates of CYFRA and SCCA are high in patients with SCC. Although the standard diagnostic procedures such as X-ray examinations, conventional tumor markers, and bronchial lavage are important for the detection of lung cancer, they are not still sensitive enough to detect lung cancer at an early clinical stage.Tyrosine kinase activity of EGFR promotes tumor cell proliferation, cell survival, angiogenesis, invasion, and metastasis, and its specific inhibition by gefitinib, a synthetic anilinoquinazoline, has been demonstr...

Background/Aim: Telomerase reverse transcriptase protein (hTERT) mRNA has been reported to be detectable by reverse transcription polymerase chain reaction (RT-PCR) in the serum of patients with breast cancer. We measured serum hTERT mRNA in patients with hepatocellular carcinoma (HCC), and examined its clinical usefulness. Methods: We performed RT-PCR to detect the expression of hTERT mRNA in 78 patients with HCC, 10 with liver cirrhosis (LC), 12 with chronic hepatitis (CH), and 34 healthy individuals without any liver diseases and cancers, and statistically analyzed the association with clinical parameters which include age, sex, etiology, Child classification, underlying liver disease, biochemical data, α-fetoprotein (α-AFP) number and size of tumor, and histological differentiation of HCC regarding HCC patients. Results: 70 of 78 (89.7%) patients with HCC, 7 of 10 (70.0%) with LC, and 5 of 12 (41.7%) with CH were positive for hTERT expression, whereas all healthy individuals were negative for it. A multivariate analysis showed that positivity of hTERT mRNA was independently associated with AFP, tumor size, and differentiation degree. Conclusions: These results suggest that this assay is sensitive enough to detect hTERT mRNA in serum, and that it would be applicable for early detection and diagnosis of HCC or other cancers by a quantitative method.

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.

These results demonstrated that combining the ACT score and percentage of predicted FEV(1), but not FE(NO,) can sufficiently stratify the risk for future exacerbations within one year.