Aberrant Methylation of MEG3 Functions as a Potential Plasma-Based Biomarker for Cervical Cancer

Methylation alterations of specific genes have recently been identified as diagnostic biomarkers for human cancers. Although MEG3 has been proved to be a tumor suppressor in cervical cancer according to our previous study, the diagnostic value of MEG3 methylation in plasma is still unknown. Therefore, the aim of this study is to identify a novel epigenetic biomarker for cervical cancer. In the current study, the level of MEG3 methylation was evaluated using methylation-specific polymerase chain reaction. The results showed that the level of MEG3 methylation was significantly higher in cervical cancer tissues and patients’ plasmas than those in adjacent normal tissues and plasmas of healthy participants respectively. Moreover, the accuracy was good enough for MEG3 methylation in plasma to discriminate CIN III patients from healthy participants. In addition, MEG3 methylation in plasma also has high discriminating power to predict HR-HPV infection and lymph node metastasis. Furthermore, hypermethylation of MEG3 in plasma was associated with worse recurrence-free and overall survival in cervical cancer patients. In conclusions, MEG3 methylation in plasma can serve as a diagnostic and prognostic biomarker for cervical cancer, providing useful information for clinical management.

[1]  Yunli Zhou,et al.  MEG3 noncoding RNA: a tumor suppressor. , 2012, Journal of molecular endocrinology.

[2]  J. Rinn,et al.  lincRNAs act in the circuitry controlling pluripotency and differentiation , 2011, Nature.

[3]  Hongtu Zheng,et al.  Low expression of novel lncRNA RP11-462C24.1 suggests a biomarker of poor prognosis in colorectal cancer , 2014, Medical Oncology.

[4]  Wun-Jae Kim,et al.  Epigenetic markers as promising prognosticators for bladder cancer , 2009, International journal of urology : official journal of the Japanese Urological Association.

[5]  J. Mattick,et al.  The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. , 2011, Cancer research.

[6]  Yali Gao,et al.  Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer , 2017, Journal of Experimental & Clinical Cancer Research.

[7]  Jing Zhao,et al.  Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. , 2005, The Journal of clinical endocrinology and metabolism.

[8]  E. Zwarthoff,et al.  DNA methylation-based biomarkers in bladder cancer , 2013, Nature Reviews Urology.

[9]  N. Sakuragi Refining insight into cervical cancer progression. , 2014, The Lancet. Oncology.

[10]  William M. Grady,et al.  Epigenetics and colorectal cancer , 2011, Nature Reviews Gastroenterology &Hepatology.

[11]  Yali Gao,et al.  Decreased expression of MEG3 contributes to retinoblastoma progression and affects retinoblastoma cell growth by regulating the activity of Wnt/β-catenin pathway , 2016, Tumor Biology.

[12]  Rui Li,et al.  The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells. , 2015, International journal of oncology.

[13]  R. Shiekhattar,et al.  Long Noncoding RNAs Usher In a New Era in the Biology of Enhancers , 2013, Cell.

[14]  A. Chinnaiyan,et al.  The Long Non-Coding RNA PCAT-1 Promotes Prostate Cancer Cell Proliferation through cMyc12 , 2014, Neoplasia.

[15]  S. Wacholder,et al.  Human papillomavirus testing in the prevention of cervical cancer. , 2011, Journal of the National Cancer Institute.

[16]  Kimberly Walter,et al.  Quantitative comparison of DNA methylation assays for biomarker development and clinical applications , 2016, Nature Biotechnology.

[17]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[18]  J. Si,et al.  Zic1 Promoter Hypermethylation in Plasma DNA Is a Potential Biomarker for Gastric Cancer and Intraepithelial Neoplasia , 2015, PloS one.

[19]  Timothy Hardy,et al.  Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease , 2016, Gut.

[20]  E. Hatzimichael,et al.  Promoter hypermethylation of the MEG3 (DLK1/MEG3) imprinted gene in multiple myeloma. , 2008, Clinical lymphoma & myeloma.

[21]  Jun Zhang,et al.  Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21 , 2016, Cancer biology & therapy.

[22]  A. Green,et al.  The IG-DMR and the MEG3-DMR at Human Chromosome 14q32.2: Hierarchical Interaction and Distinct Functional Properties as Imprinting Control Centers , 2010, PLoS genetics.