Cited 28 times since 2015 (3.1 per year) source: EuropePMC British journal of cancer, Volume 112, Issue 6, 17 3 2015, Pages 1105-1113 DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach. Hubers AJ, Heideman DA, Burgers SA, Herder GJ, Sterk PJ, Rhodius RJ, Smit HJ, Krouwels F, Welling A, Witte BI, Duin S, Koning R, Comans EF, Steenbergen RD, Postmus PE, Meijer GA, Snijders PJ, Smit EF, Thunnissen E
Background
Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer.
Methods
DNA hypermethylation of RASSF1A, APC, cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities.
Results
In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set.
Conclusions
Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer.
