Background
Early detection is essential to improve the survival and life quality of lung cancer (LC) patients. Changes of peripheral blood DNA methylation could be associated with malignancy but were mostly studied in Caucasians.
Methods
Here, in a Chinese population, we performed mass spectrometry assays to investigate the association between very early stage LC and methylation levels of RAPSN in the peripheral blood by a case–control cohort using of 221 LC patients (93.2% LC at stage I) and 285 unrelated cancer free control individuals.
Results
The odds ratios (ORs) of all CpG sites were evaluated for their risk to LC using inter-quartile analyses by logistic regression. In general, we observed an association between very early LC and decreased methylation of RAPSN_CpG_1.15 and RAPSN_CpG_3.4 (referring to Q4, OR range from 1.64 to 1.81,
p
<0.05). Stratified by gender, while hypomethylation of RAPSN_CpG_1.15, RAPSN_CpG_3.4 and RAPSN_CpG_7.14 were associated with LC in males (referring to Q4, ORs range from 1.94 to 2.31,
p
<0.05), RAPSN_CpG_2 and RAPSN_CpG_5 showed significantly lower methylation in female LC patients comparing to controls (referring to Q4, ORs range from 2.49 to 3.60,
p
<0.05). The risk of RAPSN hypomethylation to LC was enhanced by aging, and typically for people older than 55 years (referring to Q4, ORs range from 2.17 to 3.61 in six out of all 10 analyzed CpG groups,
p
<0.05).
Conclusion
Our study reveals an association between RAPSN hypomethylation in peripheral blood and LC and suggests the occurrence of altered blood-based methylation at the early stage of cancer.
e20551 Background: Early detection of lung cancer (LC) is vital for reducing of LC-related mortality. Although the screening of persons at high risk for LC by low-dose computed tomographic (LDCT) has showed an inspiring 20.0% decrease in mortality, it also comes along with a dramatically high false positive rate for distinguishing the malignant nodules from the benign nodules. Thus, it is necessary to develop a diagnostic tool with high discriminant ability for identifying malignant nodules. Methods: The methylation levels of five candidate genes were quantitatively measured via mass spectrometry. A diagnostic model was developed by blood-based methylation levels in training cohort (650 LC cases vs. 114 benign lung nodules), and further validated the performance in validation cohort (195 LC cases vs. 39 benign lung nodules) by binary logistic regression. Notably, 91.8% LC cases were collected at Stage I. Results: The methylation model of 35 CpG sites was developed and validated for LC diagnosis. This model achieved a sensitivity of 85.4% and a specificity of 92.5% in training cohort [Area Under the Curve (AUC): 0.945], and a sensitivity of 84.1% and a specificity of 97.2% in validation cohort (AUC: 0.932). The performance was well maintained in (a) Stage I subgroup (n = 447), with a sensitivity of 82.6% and a specificity of 81.6%; (b) nodule diameter ≤ 1 cm (n = 113), with a sensitivity of 80.6% and a specificity of 81.6% in validation cohort. Conclusions: This study suggests that the blood-based DNA methylation panel may provide the potential utility for early diagnosis of LC cases, which would promote early diagnosis and benefit more LC patients.
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