Liquid Biopsy Analysis Unit, Oncomet, Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain.
Faculty of Health Sciences, Universidad Autónoma de Chile, Talca, 3460000, Chile.
Cells. 2020 Feb 24;9(2):514. doi: 10.3390/cells9020514.
Natural killer cells (NK cells) play a major role in the immune response to cancer. An important element of NK target recognition is the binding of human leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIRs). Colorectal carcinoma (CRC) is one of the most common types of inflammation-based cancer. The purpose of the present study was to investigate the presence of KIR genes and HLA class I and II alleles in 1074 CRC patients and 1272 controls. We imputed data from single-nucleotide polymorphism (SNP) Illumina OncoArray to identify associations at HLA (HLA-A, B, C, DPB1, DQA1, DQB1, and DRB1) and KIRs (HIBAG and KIR*IMP, respectively). For association analysis, we used PLINK (v1.9), the PyHLA software, and R version 3.4.0. Only three SNP markers showed suggestive associations ( < 10; rs16896742, rs28367832, and rs9277952). The frequency of KIR2DS3 was significantly increased in the CRC patients compared to healthy controls ( < 0.005). Our results suggest that the implication of NK cells in CRC may not act through allele combinations in KIR and HLA genes. Much larger studies in ethnically homogeneous populations are needed to rule out the possible role of allelic combinations in KIR and HLA genes in CRC risk.
自然杀伤细胞(NK 细胞)在癌症的免疫反应中发挥着重要作用。NK 细胞靶标识别的一个重要元素是杀伤免疫球蛋白样受体(KIR)与人类白细胞抗原(HLA)I 类分子的结合。结直肠癌(CRC)是最常见的炎症相关癌症之一。本研究旨在调查 1074 例 CRC 患者和 1272 例对照中 KIR 基因和 HLA I 类和 II 类等位基因的存在情况。我们使用单核苷酸多态性(SNP)Illumina OncoArray 进行数据推断,以鉴定 HLA(HLA-A、B、C、DPB1、DQA1、DQB1 和 DRB1)和 KIR(分别为 HIBAG 和 KIR*IMP)上的关联。对于关联分析,我们使用了 PLINK(v1.9)、PyHLA 软件和 R 版本 3.4.0。只有三个 SNP 标记显示出提示性关联(<10;rs16896742、rs28367832 和 rs9277952)。与健康对照组相比,CRC 患者中 KIR2DS3 的频率显著增加(<0.005)。我们的研究结果表明,NK 细胞在 CRC 中的作用可能不是通过 KIR 和 HLA 基因中的等位基因组合来发挥的。需要在种族同源人群中进行更大规模的研究,以排除 KIR 和 HLA 基因中等位基因组合在 CRC 风险中的可能作用。