Dataset Information

Gene methylation as a powerful biomarker for detection and screening of non-small cell lung cancer in blood.

ABSTRACT: DNA methylation has been reported to become a potential powerful tool for cancer detection and diagnosis. However, the possibilities for the application of blood-based gene methylation as a biomarker for non-small cell lung cancer (NSCLC) detection and screening remain unclear. Hence, we performed this meta-analysis to evaluate the value of gene methylation detected in blood samples as a noninvasive biomarker in NSCLC. A total of 28 genes were analyzed from 37 case-control studies. In the genes with more than three studies, we found that the methylation of P16, RASSF1A, APC, RAR?, DAPK, CDH13, and MGMT was significantly associated with risks of NSCLC. The methylation statuses of P16, RASSF1A, APC, RAR?, DAPK, CDH13, and MGMT were not linked to age, gender, smoking behavior, and tumor stage and histology in NSCLC. Therefore, the use of the methylation status of P16, RASSF1A, APC, RAR?, DAPK, CDH13, and MGMT could become a promising and powerful biomarker for the detection and screening of NSCLC in blood in clinical settings. Further large-scale studies with large sample sizes are necessary to confirm our findings in the future.

SUBMITTER: Wang BH

PROVIDER: S-EPMC5458240 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Gene methylation as a powerful biomarker for detection and screening of non-small cell lung cancer in blood.

Wang Bao-Hua BH Li Yan-Yu YY Han Jin-Zhu JZ Zhou Lian-Ya LY Lv Ying-Qian YQ Zhang He-Lin HL Zhao Li L

Oncotarget 20170501 19

DNA methylation has been reported to become a potential powerful tool for cancer detection and diagnosis. However, the possibilities for the application of blood-based gene methylation as a biomarker for non-small cell lung cancer (NSCLC) detection and screening remain unclear. Hence, we performed this meta-analysis to evaluate the value of gene methylation detected in blood samples as a noninvasive biomarker in NSCLC. A total of 28 genes were analyzed from 37 case-control studies. In the genes ...[more]

PMID: 28404957

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Project description:BackgroundN6-methyladenosine (m6A) triggers a new layer of epi-transcription. However, the potential noninvasive screening and diagnostic value of peripheral blood m6A for cancer are still unknown. Here, we intend to investigate whether leukocyte m6A can be a novel biomarker for non-small-cell lung cancer (NSCLC).Materials and methodsPeripheral blood was collected from 119 NSCLC patients and 74 age-matched healthy controls. Total RNA was isolated from leukocytes for m6A measurement, and clinical information of participants was reviewed. The sensitivity, specificity, and area under the curve (AUC) of m6A for cancer diagnosis were evaluated by the receiver-operating characteristic (ROC) curve analysis. Flow cytometry and the Human Protein Atlas (HPA) database were used to characterize m6A in leukocyte differentials. Pearson's correlation was applied to indicate the relationship between m6A level and hematology variables. qPCR and bioinformatic analysis were used to identity the expression of m6A regulators in leukocyte.ResultsLeukocyte m6A was significantly elevated in 119 NSCLC patients compared with 74 healthy controls (P<0.001). We did not find significant association between m6A and age or gender. Elevated m6A level in NSCLC was associated with tumor stage (P<0.05) and tumor differentiation (P<0.05), and was significantly reduced after surgery (P<0.01). ROC curve analysis revealed that leukocyte m6A could significantly discriminate patients with lung adenocarcinoma (LUAD) (AUC=0.736, P<0.001) and lung squamous cell carcinoma (LUSC) (AUC=0.963, P<0.001) from healthy individuals. m6A displayed superior sensitivity (100%) and specificity (85.7%) for LUSC than squamous cell carcinoma (SCC) antigen and cytokeratin fragment 211 (Cyfra211). Flow cytometry analysis showed m6A modification was mainly localized on T cells and monocytes among leukocyte differentials. Leukocyte m6A was positively correlated with the number of lymphocytes and negatively correlated with monocytes in NSCLC but not in healthy controls. qPCR and bioinformatic analysis showed that elevated leukocyte m6A in NSCLC was caused by upregulated methyltransferase complex and downregulated FTO and ALKBH5.ConclusionLeukocyte m6A represents a potential noninvasive biomarker for NSCLC screening, monitoring and diagnosis.

Project description:At least seven studies have suggested that microRNA levels in whole blood can be diagnostic for lung cancer. We conducted a large bi-institutional study to validate this. Qiagen® PAXgene™ Blood miRNA System was used to collect blood and extract RNA from it for 85 pathologic stage I-IV non-small cell lung cancer (NSCLC) cases and 76 clinically-relevant controls who had a benign pulmonary mass, or a high risk of developing lung cancer because of a history of cigarette smoking or age >60 years. Cases and controls were similar for age, gender, race, and blood hemoglobin and leukocyte but not platelet levels (0.23 and 0.26 million/μl, respectively; t test P = 0.01). Exiqon® MiRCURY™ microarrays were used to quantify microRNAs in RNA isolates. Quantification was also performed using Taqman™ microRNA reverse transcription (RT)-PCR assays for five microRNAs whose lung cancer-diagnostic potential had been suggested in seven published studies. Of the 1,941 human mature microRNAs detectable with the microarray platform, 598 (31%) were identified as expressed and reliably quantified among the study's subjects. However, none of the microRNAs was differentially expressed between cases and controls (P >0.05 at false discovery rate <5% in test using empirical Bayes-moderated t statistics). In classification analyses with leave-one-out internal cross-validation, cases and controls could be identified by microRNA expression with 47% and 50% accuracy with support vector machines and top-scoring pair methods, respectively. Cases and controls did not differ for RT-PCR-based measurements of any of the five microRNAs whose biomarker potential had been suggested by seven previous studies. Additionally, no difference for microRNA expression was noticed in microarray-based microRNA profiles of whole blood of 12 stage IA-IIIB NSCLC cases before and three-four weeks after tumor resection. These findings show that whole blood microRNA expression profiles lack diagnostic value for high-risk screening of NSCLC, though such value may exist for selective sub-groups of NSCLC and control populations.

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Gene methylation as a powerful biomarker for detection and screening of non-small cell lung cancer in blood.

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Gene methylation as a powerful biomarker for detection and screening of non-small cell lung cancer in blood.

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