Amplification of human telomerase reverse transcriptase gene as a diagnostic marker in lung cancer

ABSTRACT

Analysis of circulating DNA or RNA in plasma can provide a useful marker for earlier lung cancer detection. This study was designed to assess the sensitivity and specificity of a quantitative molecular assay of circulating RNA to identify patients with lung cancer with different grades. The amount of plasma RNA was determined through the use of real-time quantitative polymerase chain reaction [PCR] amplification of the human telomerase reverse transcriptase gene [hTERT] in 19 non-small-cell lung cancer patients and 10 age and sex matched controls. Performance of the assay was calculated through the receiver operating characteristic [ROC] curve. The hTERT mRNA ratio in cancer lung patients showed a mean of 196.34 +/- 307.23 which was higher compared to that of the controls 1.24 +/- 0.80; this difference was statistically highly significant where P<0.01. The median concentration of circulating plasma RNA in patients was higher than the value detected in controls [71.70 v 1.149 ratio]. Plasma RNA was a strong risk factor for lung cancer; concentrations in the patients were associated with a 62-fold higher risk than were those in the controls. The point of the best cut-off value was at 2.24 where sensitivity was 73.7% and specificity was 90%. The area under the ROC curve was 0.704. This study shows that higher levels of free circulating RNA can be detected in patients with lung cancer compared with disease-free heavy smokers by a PCR assay, and suggests a new, noninvasive approach for early detection of lung cancer. Levels of plasma RNA is recommended to be measured as it could also identify higher-risk individuals for lung cancer screening and chemoprevention trials