LINE-1 methylation in the peripheral blood mononuclear cells of cancer patients

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• 作者：Nakarin Kitkumthorn^a ; Time Tuangsintanakul^b ; ^c ; Prakasit Rattanatanyong^b ; Danai Tiwawech^c ; ^{tdnai@hotmail.com} ; Apiwat Mutirangura^b ; ^{mapiwat@chula.ac.th}
• 关键词：LINE-1 methylation ; COBRA LINE-1 ; Level and pattern ; Peripheral blood mononuclear cells ; Cancer
• 刊名：Clinica Chimica Acta
• 出版年：2012
• 期刊代码：54_00098981
• 类别：med
• 出版时间：18 May, 2012
• 卷：413
• 期：9-10
• 页码：869-874
• 文件大小：860 K

摘要

Background

Recently, we classified LINE-1 loci according to their methylation statuses and found that the percentage of hypomethylated LINE-1 loci (^uC^uC) can differentiate between the peripheral blood mononuclear cells (PBMCs) of oral cancer patients and normal controls with a higher specificity and sensitivity than overall methylation levels. Here, we evaluated the LINE-1 methylation levels and patterns in PBMCs from patients with cancers of the nasopharynx, lung, liver, bile duct, breast and colon.

Methods

Combined Bisulfite Restriction Analysis (COBRA) of LINE-1 loci was performed to examine the LINE-1 methylation statuses of PBMCs from 216 cancer patients with 6 different types of cancer compared with 144 normal controls.

Results

Only colorectal and nasopharyngeal cancer samples were found to have lower levels of overall LINE-1 methylation compared with normal controls (p < 0.0001 and p = 0.0022). However,%^uC^uC in cancers of the colon, liver, lung and nasopharynx was significantly higher compared with normal controls (p < 0.0001, p < 0.0001, p = 0.01 and p = 0.001, respectively). Furthermore, ROC curve analyses of these four cancer types also demonstrated the potential of%^uC^uC as a biomarker for cancer diagnosis.

Conclusion

Changes in the levels and patterns of genome-wide methylation of PBMCs are associated with cancer risk. For LINE-1,%^uC^uC is a more effective tumour marker for determining cancer risk than overall methylation levels.