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基质金属蛋白酶9启动子多态性(-1562 C/T)不影响乳腺癌患者血清中可溶性MICA和MICB水平

MMP9 Promoter Polymorphism (-1562 C/T) Does not Affect the Serum Levels of Soluble MICB and MICA in Breast Cancer.

作者信息

Bargostavan Mohammad Hasan, Eslami Gilda, Esfandiari Nasrin, Shams Shahemabadi Ali

机构信息

Department of Immunology, International Campus, Shahid Sadoughi University Medical Sciences, Yazd, Iran, e-mail:

出版信息

Iran J Immunol. 2016 Mar;13(1):45-53.

Abstract

BACKGROUND

The role of Matrix Metalloproteinase 9 (MMP9) in tumor invasion and progression is prominent. A single nucleotide polymorphism (SNP) in the promoter region of MMP9 (-1562 C/T) increases the transcription and expression of this gene. On the other hand, MHC class I chain-related protein A and B (MICA/B) in soluble forms may impair tumor immunogenicity by reducing Natural Killer Group 2D (NKG2D) densities on NK cells and MMP9 enzyme activity has a prominent role in shedding of MICA/B.

OBJECTIVES

To investigate the association between MMP9 (-1562 C/T) polymorphism and serum MICA/B level in breast cancer patients.

METHODS

In this case-control study, 105 patients with breast cancer and 100 healthy age-matched women were selected from Yazd hospitals, Iran. The polymorphism of MMP9 (-1562 C/T) was determined by PCR-RFLP. Concentration of MICB and MICA in the sera of breast cancer patients and healthy women were measured using ELISA method.

RESULTS

The frequency of CC, CT and TT genotypes and T allele of the MMP9 (-1562 C/T) did not show significant differences between breast cancer patients and healthy donors (p>0.05). On the other hand, the mean serum levels of MICB and MICA were significantly elevated in patients compared with healthy individuals (p<0.05). In patients with MMP9CC genotype, the mean serum MICB concentration was significantly higher than those patients with CT polymorphism (p<0.05). Although the mean of blood MICA concentration in patients with the CT genotype was higher than those patients with CC genotype, the difference was not statistically significant.

CONCLUSION

The T allele of the MMP9 (-1562 C/T) does not show a correlation with serum levels of MICA and MICB in breast cancer patients.

摘要

背景

基质金属蛋白酶9(MMP9)在肿瘤侵袭和进展中作用显著。MMP9启动子区域的单核苷酸多态性(SNP)(-1562 C/T)可增加该基因的转录和表达。另一方面,可溶性的主要组织相容性复合体I类链相关蛋白A和B(MICA/B)可能通过降低自然杀伤细胞2D(NKG2D)在自然杀伤细胞上的密度来损害肿瘤免疫原性,且MMP9酶活性在MICA/B的脱落中起重要作用。

目的

研究乳腺癌患者中MMP9(-1562 C/T)多态性与血清MICA/B水平之间的关联。

方法

在这项病例对照研究中,从伊朗亚兹德医院选取了105例乳腺癌患者和100名年龄匹配的健康女性。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)确定MMP9(-1562 C/T)的多态性。采用酶联免疫吸附测定(ELISA)法测量乳腺癌患者和健康女性血清中MICB和MICA的浓度。

结果

MMP9(-1562 C/T)的CC、CT和TT基因型频率以及T等位基因在乳腺癌患者和健康供者之间未显示出显著差异(p>0.05)。另一方面,与健康个体相比,患者血清中MICB和MICA的平均水平显著升高(p<0.05)。在MMP9 CC基因型患者中,血清MICB平均浓度显著高于CT多态性患者(p<0.05)。虽然CT基因型患者的血液MICA平均浓度高于CC基因型患者,但差异无统计学意义。

结论

MMP9(-1562 C/T)的T等位基因与乳腺癌患者血清MICA和MICB水平无相关性。

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