Clinicopathologic significance of telomerase activity and hTERT mRNA expression in non-small cell lung cancer.
Telomerase has been reported to be a novel diagnostic marker for malignant diseases and has been recently proven to be composed of three main components, hTR (human telomerase RNA component), TP1 (telomerase-associated protein 1) and hTERT (human telomerase reverse transcriptase), the last of which plays a key role in telomerase activation. In the present study, quantitative levels of telomerase activity and hTERT gene mRNA (hTERT) expression were analyzed in cancerous and non-cancerous lung tissues of 62 lung cancer patients by telomeric repeat amplification protocol and reverse transcription-PCR, respectively. The telomerase expression levels of each group of tissue samples were compared with clinicopathologic variables. Telomerase activity and hTERT were detected in cancerous tissues (75.8 and 75.8%, respectively), while these parameters were not observed in any non-cancerous tissues. In quantitative assessment of telomerase expression, both telomerase activity and hTERT were significantly correlated with lymph node metastasis (N0 vs. N1+2, P<0.05). Telomerase activity also correlated with tumor cell differentiation and stage classification (P<0.05), but did not correlate with other clinicopathologic variables. The disease-free survival in patients with lung cancer demonstrated that patients with hTERT-positive tumor survived for a significantly shorter period than those with hTERT-negative tumor (P=0.0334). Since hTERT levels are correlated with N factor which represents the true aggressiveness of patients' disease concerning the evaluation of clinical outcome, hTERT was found to be one of the important markers revealing biological malignant potentials for lung cancer.
Hara
H
H
Department of Thoracic and Cardiovascular Surgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Yamashita
K
K
Shinada
J
J
Yoshimura
H
H
Kameya
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase