|
|
|
| Clinical Importance of Methylation Status of Gene Promoter HOXA5 and HOXA10 in Gastric Cancer |
| FANG Zhi-xue, HUANG Zhong-cheng |
| Department of anus colorectal surgery, Hunan provincial people's hospital,410005 China |
|
|
|
Abstract 【Objective】To investigate the methylation status of the gene promoters HOXA5 and HOXA10 and its relationship with clinical pathology in gastric cancer. 【Methods】Methylation status of gene promoters HOXA5 and HOXA10 in 51 of cases of gastric cancer tissues and normal mucosa tissues were detected by methylation-specific PCR (MSP). 【Results】 1.The methylation rate of HOXA5 gene promoter in gastric cancer tissues (74.5%) was higher than that in normal mucosa tissues (37.3%),the difference was statistically significant (χ2=14.356,P=0.000). The methylation rate of HOXA5 gene promoter was negatively related to the tumor grade (χ2=4.311,P=0.038), the degree of invasion (χ2=5.669,P=0.017), the lymphatic metastasis (χ2=9.349,P=0.002) and tumor stage (χ2=16.023,P=0.000), but was not related to age or gender (mean P>0.05); 2. The methylation rate of HOXA10 gene promoter in gastric cancer tissues (68.6%)was higher than that in the normal mucosa tissues (41.2%),the difference was statistically significant (χ2=7.761,P=0.009). The methylation rate of HOXA10 gene promoter was negatively related to the tumor grade (χ2=5.304,P=0.021), the degree of invasion (χ2=15.457,P=0.000) and lymphatic metastasis (χ2=6.157,P=0.013), but was not related to the tumor stage, the age nor the gender (mean P>0.05); 3.The methylation status of HOXA5 gene promoter was negatively associated with its protein expression(r=-0.495,P=0.000), and so was HOXA10 (r=-0.343,P=0.000). There was a positively relationship between the methylation rate of two gene promoters (r=0.751,P=0.000). 【Conclusion】HOXA5 and HOXA10 gene promoters were highly methylated in gastric cancer tissues and were negatively related with their protein expression. DNA methylation may be one of important regulatory mechanisms underlying gene expression changes.
|
|
Received: 30 October 2016
|
|
|
|
|
|
[1] 郑朝旭,郑荣寿,张思维,等.中国 2010 年胃癌发病与死亡分析[J].中国肿瘤,2014,23(10): 795-800.
[2] 陈万青,张思维,曾红梅,等.中国2010年恶性肿瘤发病与死亡[J].中国肿瘤,2014,24(1): 1-10.
[3] Toyota M,Ahuja N,Ohe-Toyota M,et al. CpG island methylator phenotype in colorectal cancer[J].Proc Natl Acad Sci USA,1999, 96(15): p. 8681-8686.
[4] Toyota M,Ahuja N,Suzuki H,et al. Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype[J].Cancer Res,1999,59(21):5438-5442.
[5] Vertino PM,Yen RW,Gao J,et al. De novo methylation of CpG island sequences in human fibroblasts overexpressing DNA (cytosine-5-)-methyltransferase [J].Mol Cell Biol,1996, 16(8):4555-4565.
[6] Chen FY,Harris LC,Remack JS,et al. Cytoplasmic sequestration of an O6-methylguanine-DNA methyltransferase enhancer binding protein in DNA repair-deficient human cells [J].Proc Natl Acad Sci USA,1997, 94(9):4348-4353.
[7] Mummaneni P,Yates P,Simpson J,et al. The primary function of a redundant Sp1 binding site in the mouse aprt gene promoter is to block epigenetic gene inactivation [J].Nucleic Acids Res,1998, 26(22):5163-5169.
[8] Choi IS,Wu TT. Epigenetic alterations in gastric carcinogenesis [J].Cell Res,2005,15(4):247-254.
[9] Liang G,Salem CE,Yu MC,et al. DNA methylation differences associated with tumor tissues identified by genome scanning analysis [J].Genomics,1998, 53(3):260-268.
[10] Yang YC,Wang SW,Wu IC,et al. A tumorigenic homeobox (HOX) gene expressing human gastric cell line derived from putative gastric stem cell [J].Eur J Gastroenterol Hepatol,2009,21(9):1016-1023.
[11] Sentani K,Oue N,Naito Y,et al. Upregulation of HOXA10 in gastric cancer with the intestinal mucin phenotype: reduction during tumor progression and favorable prognosis [J].Carcinogenesis,2012,33(5): 1081-1088. |
|
|
|
2016, Vol. 33 
