HLA-KIR-MICA基因及其NK受体免疫应答与三阴性乳腺癌的相关性

Correlation Between HLA-KIR-MICA Gene and NK Receptor Immune Response and Triple-Negative Breast Cancer

[目的]探讨HLA-KIR-MICA基因及其自然杀伤细胞(natural killer cell,NK)受体免疫应答与三阴性乳腺癌(triple negative breast cancer,TNBC)的相关性。[方法]选取2018年2月至2019年2月我院治疗的TNBC女性患者400例,同时选取100例健康成年女性作为对照组。采用HLA分型法检测HLA等位基因、MICA基因和KIR基因;采用Real-time PCR法检测HLA等位基因、MICA基因和KIR基因转录水平;检测NK细胞免疫球蛋白经MICA检测后的表达量差异及与预后的关系。[结果] TNBC患者的等位基因中,HLA-KIR*17(48.5%vs.28.0%,P<0.001)、HLA-KIR*1003 (45.3%vs. 34.0%,P=0.042)、HLA-KIR*14 (32.5%vs. 19.0%,P=0.008)、MICA*13(40.8%vs. 20.0%,P<0.001)、MICA*20(33.3%vs. 15.0%,P<0.001)基因占比均高于对照组;HLA-KIR*02 (16.5%vs. 49.0%,P<0.001)、HLA-KIR*12 (48.3%vs. 77.0%,P<0.05)、MICA*04(10.8%vs. 44.0%,χ2=61.538,P<0.001)、MICA*17(34.8%vs. 69.0%,P<0.001)和MICA*15(33.8%vs. 66.0%,P<0.001)基因占比均低于对照组;两组HLA-KIR*0801和MICA*0601基因占比差异无统计学意义(P>0.05)。与完全缓解(CR)+部分缓解(PR)比,稳定(SD)+疾病进展(PD)的HLA-KIR*17、HLA-KIR*1003、MICA*13、MICA*20基因占比降低(均P <0.05),HLAKIR*14、HLA-KIR*02、HLA-KIR*12、MICA*04、MICA*17和MICA*15基因占比增高(均P<0.05)。[结论] HLA-KIR*17、HLA-KIR*1003、MICA*13、MICA*20及HLA-KIR*14、HLAKIR*02、HLA-KIR*12、MICA*04、MICA*17、MICA*15等位基因可能与TNBC发生相关,可能起到抑制或延缓TNBC发生的作用。

[Objective] To investigate the relationship between HLA-KIR-MICA gene and natural killer cell(NK) receptor immune response and triple negative breast cancer(TNBC). [Methods]From February 2018 to February 2019,400 female TNBC patients who received treatment in our hospital were selected,while 100 healthy adult female were selected as the control group. Realtime PCR was used to detect the transcription level of HLA alleles,MICA gene and KIR gene.The expression difference of NK cell immunoglobulin after MICA detection and its relationship with prognosis was detected. [Results] Among the alleles of TNBC patients,HLA-KIR*17(48.5%vs 28.0%,P<0.001),HLA-KIR*1003(45.3% vs 34.0%,P=0.0042),HLA-KIR*14(32.5% vs 19.0%,P=0.0008),MICA*13(40.8 % vs 20.0%,P<0.001),MICA*20(33.3% vs 15.0%,P<0.001) gene ratios were higher than that in control group. HLA-KIR* 02(16.5% vs 49.0%%,P <0.001),HLA-KIR*12(48.3% vs 77.0%,P <0.001),MICA*04(10.8% vs 44.0%,P <0.001),MICA*17(34.8% vs 69.0%,P <0.001) and MICA*15(33.8% vs 66.0%,P <0.001) ratios were lower than that in control group. HLA-KIR*0801 and MICA*0601 showed no significant difference in the proportion of genes(P>0.05). Compared with CR+PR group,HLA-KIR*17,HLA-KIR*1003,MICA*13,MICA*20 gene proportions in SD+PD group were significantly reduced(P<0.05),HLA-KIR*14,KIR*02,HLA-KIR*12,MICA*04,MICA*17 and MICA*15 genes were significantly increased(P<0.05). [Conclusion] HLA-KIR*17,HLA-KIR*1003,MICA*13,MICA*20 and HLA-KIR*14,HLA-KIR*02,HLA-KIR*12,MICA*04,MICA*17,MICA*15 allele may be related to the occurrence of TNBC,and may play a role in suppressing or delaying the occurrence of TNBC.