The Evaluation Value of Methylation Status of CpG Island of SFRP1 and LINE1 Gene Promoter Area in the Prognosis of Hepatocellular Carcinoma

HUANG Yuan, WEI Ling, SUN Ai-min. et al

Abstract

To investigate the relationship between aberrant promoter CpG islands methylation status of secreted frizzled related protein 1 (SFRP1) and long intersper sed nuclear element 1 (LINE1) gene and clinicopathologic parameters to determine their prognosis value for hepatocellular carcinoma (HCC). Methods 105 cases of HCC and 50 cases of normal people plasma were collected, and then the promoter hypermethylation status of SFRP1 and hypormethylation status of LINE1 were examined by methylation specific PCR (MSP); The relationship between SFRP1/LINE1 methylation status and patients’ clinicopathologic factors was analyzed; The association between SFRP1/LINE1 methylation status and disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and multivariate Cox regression. Results SFRP1 gene promoter CpG islands hypermethylation and LINE1 gene promoter CpG islands hypomethylation were found in 59.05% (62/105) and 66.67% (70/105) of 105 cancerous plasma cases, repectively, SFRP1 hypermethylation status and LINE1 hypomethylation status in plasma of HCC account for 43.81%(62/105) and no positive methylation cases were detected in normal cases; The hypermethylation status of SFRP1 and hypomethylation status of LINE1 gene were related with HBsAg and α-fetoprotein (AFP) level; There was statistically significant difference between CpG islands hypermethylation of two genes and disease-free survival rate and overall survival rate; The group patients with SFRP1 hypermethylation positive and LINE1 hypomethylation positive demonstrated the worst prognosis while the group with SFRP1 hypermethylation negative and LINE1 hypomethylation negative had the best prognosis. Conclusion The promoter methylation of SFRP1 and LINE1 is correlated with the occurrence and development of HCC. SFRP1 and LINE1 might be potential and reliable biomarkers for predicting prognosis in HCC patients.

 

Keywords:  Hepatocellular carcinoma, SFRP1 LINE1, Methylation, Prognosis 

 

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References


LIU JB, ZHANG YX, ZHOU SH, et al. CpG island methylator phenotype in plasma is associated with hepatocellular carcinoma prognosis. World J Gastroenterol, 2011,17(42);4718-4724.

LIU YH, WU JZ. HU XQ, et al. Diagnosis of hepatocellular carcinoma by using methylation specific-PCR. Wuhan University Journal of Natural Sciences, 2007, 12 (3 ): 558-562.

LEE HC, KIM M, WANDS JR. Wnt/Frizzled signaling in hepatocellular carcinoma. Front Biosci,2006( 11): 1901-1915.

SHIH YL, SH YU RY, HSIEH CB, et al, Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma. Cancer,2006, 107(3);579-590.

CADIQAN KM, NUSSE R. Wnt signaling: a common theme in animal development. Genes Dev,1997,11(24);3286-3305. ZONG Y, STANGER BZ. Molecular mechanisms of bile duct development. Int J Biochem Cell Biol,2011,43(2); 257- 264.

LAVIE L, MALDENER E, BROUHA B, et al. The human LI promoter; variable transcription initiation sites and a major impact of upstream flanking sequence on promoter activity. Genome Res,2004,14( 11):2253-2260.

ALVES G, TATRO A, FANNING T. Differential methylation of human LINE-1 retrotransposons in malignant cells. Gene,1996,176(1/2) ;39-44.

TAKAHARA T. OHSUMI T, KUROMITSU J. et al. Dysfunction of the Orleans reeler gene arising from exon skipping due to transposition of a full-length copy of an active LI sequence into the skipped exon. Hum Mol Genet, 1996, 5(7); 989-993.

TAKADAT, YAG1 Y, MAEKITA T, et al. Methylation- associated silencing of the Wnt antagonist SFRP1 gene in human ovarian cancers. Cancer Sci,2004,95(9) :741-744.

WANG GS, GAO J, HUANG HL, et al. Expression of a LINE-1 endonuclease variant in gastric cancer; its association with clinicopathological parameters. BMC Cancer, 2013, 13 (265):1471-2407.

THORGEIRSSON SS, GRISHAM JW. Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet. 2002,31(4):339-346.

SHIH YL. SHYU RY. HSIEH CB, el at. Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma. Cancer. 2006.107(3):579-590.

CHALITCHAGORN K. SHUANGSHOTI S. HOURPAI N. et al. Distinctive pattern of LINE-1 methylation level in normal tissues and the association with carcinogenesis. Oncogene.2004.23(54):8841-884 6.

JI F. FU SJ. SHEN SL. et al. The prognostic value of combined TGF-pi and ELF in hepatocellular carcinoma. BMC Cancer. 2015 ( 15 ); 116 [ 2015-10-18 ]. https;//www. ncbi. nlm. nih. gov/pmc/articles/PMC4359586/. doi; 10.1186/sl2885-015-l127-y.


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