Early Detection of Lung Cancer using DNA Promoter Hypermethylation in Plasma and Sputum
Menée auprès de 150 patients atteints d'un cancer du poumon non à petites cellules de stade I à IIA sans envahissement ganglionnaire et auprès de 60 témoins, cette étude évalue la performance d'une technique, consistant à rechercher dans des échantillons de plasma ou de crachats une hyperméthylation du promoteur de six gènes (SOX17, TAC1, HOXA7, CDO1, HOXA9 et ZFP42) à l'aide d'une PCR quantitative en temps réel, pour diagnostiquer précocement la maladie
Purpose : CT screening can reduce death from lung cancer. We sought to improve the diagnostic accuracy of lung cancer screening using ultrasensitive methods and a lung cancer specific gene panel to detect DNA methylation in sputum and Plasma.
Experimental Design : This is a case-control study of subjects with suspicious nodules on CT imaging. Plasma and sputum were obtained pre-operatively. Cases (n=150) had pathological confirmation of node negative (stage I and IIA) non-small cell lung cancer. Controls (n=60) had non-cancer diagnoses. We detected promoter methylation using quantitative methylation-specific real-time PCR and Methylation on Beads for cancer-specific genes (SOX17, TAC1, HOXA7, CDO1, HOXA9, and ZFP42).
Results : DNA methylation was detected in plasma and sputum more frequently in people with cancer compared to controls (p<0.001) for 5 of 6 genes. The sensitivity and specificity for lung cancer diagnosis using the best individual genes was 63-86% and 75-92% in sputum respectively and 65-76% and 74-84% in plasma. A three-gene combination of the best individual genes has sensitivity and specificity of 98% and 71% using sputum and 93% and 62% using plasma. Area under the Receiver Operating Curve for this panel was 0.89 95% CI (0.80-0.98) in sputum and 0.77 95% CI (0.68-0.86) in plasma. Independent blinded random forest prediction models combining gene methylation with clinical information correctly predicted lung cancer in 91% of subjects using sputum detection and 85% of subjects using plasma detection.
Conclusions : High diagnostic accuracy for early stage lung cancer can be obtained using methylated promoter detection in sputum or plasma.
Clinical Cancer Research , résumé, 2015