Zhiping Yang1, Weibo Qi2, Li Sun2, Hui Zhou2, Biliu Zhou2, Yi Hu3. 1. Department of Oncology, The First Affiliated Hospital of Jiaxing University, Zhejiang, China. 2. Department of Clinical Laboratory, The First Affiliated Hospital of Jiaxing University, Zhejiang, China. 3. Department of Chest Surgery, The First Affiliated Hospital of Jiaxing University, Zhejiang, China.
Abstract
BACKGROUND: Lung cancer is still the deadliest cancer in the world, but early diagnosis cannot be achieved because of the limitations of diagnostic methods. DNA methylation has been proven to be a potentially powerful tool for cancer detection and diagnosis over the past decade. OBJECTIVES: We explored whether free DNA methylation in plasma can be a reliable biomarker for noninvasive lung cancer detection. MATERIAL AND METHODS: We detected the methylation of 8 genes in plasma-free DNA of patients with pulmonary space-occupying lesions using real-time quantitative methylation-specific polymerase chain reaction (QMSP). Among the 50 selected patients, 39 were confirmed using pathological analysis as having early lung cancer and 11 had an inflammatory pseudotumor. RESULTS: The QMSP detection showed that the methylation levels of 8 genes in the patients were significantly higher than in the non-lung cancer group. The methylation level of CALCA was the highest and the methylation level of HOXA9 was the lowest. Methylation of RASSF1A, CDKN2A and DLEC1 occured only in lung cancer patients, while methylation of CALCA, CDH13, PITX2, HOXA9, and WT1 occured not only in lung cancer patients, but also in non-lung cancers. The specificity reached 95~100%, whether for a single gene or overall, but the sensitivity was relatively low for each gene. The sensitivity can reach 72% if the methylation of any of the 8 genes is positive and the overall specificity was 91%. The positive and negative predictive values were 96% and 60%, respectively. CONCLUSIONS: Quantitative detection of DNA methylation in plasma is a potential method for early diagnosis of lung cancer.
BACKGROUND:Lung cancer is still the deadliest cancer in the world, but early diagnosis cannot be achieved because of the limitations of diagnostic methods. DNA methylation has been proven to be a potentially powerful tool for cancer detection and diagnosis over the past decade. OBJECTIVES: We explored whether free DNA methylation in plasma can be a reliable biomarker for noninvasive lung cancer detection. MATERIAL AND METHODS: We detected the methylation of 8 genes in plasma-free DNA of patients with pulmonary space-occupying lesions using real-time quantitative methylation-specific polymerase chain reaction (QMSP). Among the 50 selected patients, 39 were confirmed using pathological analysis as having early lung cancer and 11 had an inflammatory pseudotumor. RESULTS: The QMSP detection showed that the methylation levels of 8 genes in the patients were significantly higher than in the non-lung cancer group. The methylation level of CALCA was the highest and the methylation level of HOXA9 was the lowest. Methylation of RASSF1A, CDKN2A and DLEC1 occured only in lung cancerpatients, while methylation of CALCA, CDH13, PITX2, HOXA9, and WT1 occured not only in lung cancerpatients, but also in non-lung cancers. The specificity reached 95~100%, whether for a single gene or overall, but the sensitivity was relatively low for each gene. The sensitivity can reach 72% if the methylation of any of the 8 genes is positive and the overall specificity was 91%. The positive and negative predictive values were 96% and 60%, respectively. CONCLUSIONS: Quantitative detection of DNA methylation in plasma is a potential method for early diagnosis of lung cancer.
Entities:
Keywords:
QSMP; early diagnosis; lung cancer; plasma-free DNA
Authors: Sara Witting Christensen Wen; Rikke Fredslund Andersen; Torben Frøstrup Hansen; Christa Haugaard Nyhus; Henrik Hager; Ole Hilberg; Anders Jakobsen Journal: Transl Lung Cancer Res Date: 2021-02