LINE-1 Methylation in Peripheral Blood Leukocytes and Clinical Characteristics and Prognosis of Prostate Cancer Patients

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Dec 8

PMID 29212206

Citations 5

Authors

Yuyan Han

Junfeng Xu

Jeri Kim

Xifeng Wu

Jian Gu

Affiliations

Soon will be listed here.

Abstract

Global DNA methylation of long interspersed nucleotide elements (LINE-1) in leukocytes has been suggested to be a risk factor for a few cancers. There has been no report of LINE-1 methylation in leukocytes as a risk factor for aggressive prostate cancer at diagnosis and prognosis after treatments. In this study, we measured the leukocyte DNA methylation of LINE-1 in 795 PCa patients and compared the methylation levels across different clinical subgroups. We then determined the association of LINE-1 methylation in leukocytes with clinicopathological variables at diagnosis using logistic regression analysis and biochemical recurrence in patients receiving active treatments (prostatectomy and radiotherapy) using Cox proportional hazard model after adjusting for age, BMI, smoking status, pack year, D'Amico risk groups, and treatments. Overall, the DNA methylation of LINE-1 was not associated with the risk of being diagnosed with high-risk prostate cancer or the risk of biochemical recurrence upon active treatments. Future studies are warranted to investigate other types of repetitive element methylation and longitudinal changes of global methylation in relation to prostate cancer risk and prognosis.

Citing Articles

LINE-1 cfDNA Methylation as an Emerging Biomarker in Solid Cancers.

Gezer U, Ozgur E, Yoruker E, Polatoglou E, Holdenrieder S, Bronkhorst A Cancers (Basel). 2024; 16(22).

PMID: 39594682 PMC: 11592170. DOI: 10.3390/cancers16223725.

Epigenome-Wide Association Study of Prostate Cancer in African Americans Identifies DNA Methylation Biomarkers for Aggressive Disease.

Xu Y, Tsai C, Chang W, Han Y, Huang M, Pettaway C Biomolecules. 2021; 11(12).

PMID: 34944472 PMC: 8698937. DOI: 10.3390/biom11121826.

Genome-wide DNA methylation profiling of leukocytes identifies CpG methylation signatures of aggressive prostate cancer.

Han Y, Zhang M, Xu J, Li J, Xu Y, Thompson T Am J Cancer Res. 2021; 11(3):968-978.

PMID: 33791167 PMC: 7994169.

RRBP1 is highly expressed in prostate cancer and correlates with prognosis.

Li T, Wang Q, Hong X, Li H, Yang K, Li J Cancer Manag Res. 2019; 11:3021-3027.

PMID: 31118771 PMC: 6503199. DOI: 10.2147/CMAR.S186632.

LINE-1 ORF-1p enhances the transcription factor activity of pregnenolone X receptor and promotes sorafenib resistance in hepatocellular carcinoma cells.

Chen Y, Zeng Q, Liu X, Fu J, Zeng Z, Zhao Z Cancer Manag Res. 2018; 10:4421-4438.

PMID: 30349375 PMC: 6188112. DOI: 10.2147/CMAR.S176088.

References

Eden A, Gaudet F, Waghmare A, Jaenisch R . Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 2003; 300(5618):455. DOI: 10.1126/science.1083557. View

Zhu Z, Hou L, Bollati V, Tarantini L, Marinelli B, Cantone L . Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. Int J Epidemiol. 2010; 41(1):126-39. PMC: 3304518. DOI: 10.1093/ije/dyq154. View

Ogino S, Kawasaki T, Nosho K, Ohnishi M, Suemoto Y, Kirkner G . LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer. Int J Cancer. 2008; 122(12):2767-73. PMC: 2630175. DOI: 10.1002/ijc.23470. View

Choo R, Danjoux C, Gardner S, Morton G, Szumacher E, Loblaw D . Efficacy of salvage radiotherapy plus 2-year androgen suppression for postradical prostatectomy patients with PSA relapse. Int J Radiat Oncol Biol Phys. 2009; 75(4):983-9. DOI: 10.1016/j.ijrobp.2008.12.049. View

Zelic R, Fiano V, Grasso C, Zugna D, Pettersson A, Gillio-Tos A . Global DNA hypomethylation in prostate cancer development and progression: a systematic review. Prostate Cancer Prostatic Dis. 2014; 18(1):1-12. DOI: 10.1038/pcan.2014.45. View

Li J, Huang Q, Zeng F, Li W, He Z, Chen W . The prognostic value of global DNA hypomethylation in cancer: a meta-analysis. PLoS One. 2014; 9(9):e106290. PMC: 4153632. DOI: 10.1371/journal.pone.0106290. View

Valdes-Mora F, Clark S . Prostate cancer epigenetic biomarkers: next-generation technologies. Oncogene. 2014; 34(13):1609-18. DOI: 10.1038/onc.2014.111. View

Park S, Seo A, Jung H, Gwak J, Jung N, Cho N . Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer. PLoS One. 2014; 9(6):e100429. PMC: 4074093. DOI: 10.1371/journal.pone.0100429. View

Siegel R, Miller K, Jemal A . Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1):7-30. DOI: 10.3322/caac.21387. View

10.

Rodic N, Burns K . Long interspersed element-1 (LINE-1): passenger or driver in human neoplasms?. PLoS Genet. 2013; 9(3):e1003402. PMC: 3610623. DOI: 10.1371/journal.pgen.1003402. View

11.

Barry K, Moore L, Liao L, Huang W, Andreotti G, Poulin M . Prospective study of DNA methylation at LINE-1 and Alu in peripheral blood and the risk of prostate cancer. Prostate. 2015; 75(15):1718-25. PMC: 4535169. DOI: 10.1002/pros.23053. View

12.

Karami S, Andreotti G, Liao L, Pfeiffer R, Weinstein S, Purdue M . LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk. Epigenetics. 2015; 10(4):282-92. PMC: 4622590. DOI: 10.1080/15592294.2015.1006505. View

13.

Nan H, Giovannucci E, Wu K, Selhub J, Paul L, Rosner B . Pre-diagnostic leukocyte genomic DNA methylation and the risk of colorectal cancer in women. PLoS One. 2013; 8(4):e59455. PMC: 3613344. DOI: 10.1371/journal.pone.0059455. View

14.

Adalsteinsson B, Gudnason H, Aspelund T, Harris T, Launer L, Eiriksdottir G . Heterogeneity in white blood cells has potential to confound DNA methylation measurements. PLoS One. 2012; 7(10):e46705. PMC: 3465258. DOI: 10.1371/journal.pone.0046705. View

15.

Ikeda K, Shiraishi K, Eguchi A, Shibata H, Yoshimoto K, Mori T . Long interspersed nucleotide element 1 hypomethylation is associated with poor prognosis of lung adenocarcinoma. Ann Thorac Surg. 2013; 96(5):1790-4. DOI: 10.1016/j.athoracsur.2013.06.035. View

16.

Heiss J, Brenner H . Impact of confounding by leukocyte composition on associations of leukocyte DNA methylation with common risk factors. Epigenomics. 2017; 9(5):659-668. DOI: 10.2217/epi-2016-0154. View

17.

Liu J, Hesson L, Meagher A, Bourke M, Hawkins N, Rand K . Relative distribution of folate species is associated with global DNA methylation in human colorectal mucosa. Cancer Prev Res (Phila). 2012; 5(7):921-9. DOI: 10.1158/1940-6207.CAPR-11-0577. View

18.

Joyce B, Gao T, Zheng Y, Liu L, Zhang W, Dai Q . Prospective changes in global DNA methylation and cancer incidence and mortality. Br J Cancer. 2016; 115(4):465-72. PMC: 4985350. DOI: 10.1038/bjc.2016.205. View

19.

Kitkumthorn N, Tuangsintanakul T, Rattanatanyong P, Tiwawech D, Mutirangura A . LINE-1 methylation in the peripheral blood mononuclear cells of cancer patients. Clin Chim Acta. 2012; 413(9-10):869-74. DOI: 10.1016/j.cca.2012.01.024. View

20.

Stephenson A, Kattan M, Eastham J, Dotan Z, Bianco Jr F, Lilja H . Defining biochemical recurrence of prostate cancer after radical prostatectomy: a proposal for a standardized definition. J Clin Oncol. 2006; 24(24):3973-8. DOI: 10.1200/JCO.2005.04.0756. View