Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
Department of Tropical Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Asian Pac J Cancer Prev. 2023 Sep 1;24(9):3213-3219. doi: 10.31557/APJCP.2023.24.9.3213.
Chronic Opisthorchis viverrini (OV) infection is the cause of advanced periductal fibrosis (APF), subsequently leading to cholangiocarcinoma (CCA). Natural killer (NK) cells can kill hepatic stellate cells (HSCs), the initiating cells for fibrosis formation, by using the interaction between the natural killer group 2 member D (NKG2D) receptor and its ligand on the HSCs. This can inhibit the fibrosis formation. Major histocompatibility complex class I chain-related A (MICA) is the ligand of the NKG2D receptor and has highly polymorphic characteristics that are involved in NKG2D binding and NK cell activation. This study aimed to investigate the polymorphism of MICA in OV-induced fibrosis.
MICA typing was performed by polymerase chain reaction- sequence specific primer (PCR-SSP) and sequencing in two groups: OV infection without fibrosis (N = 99) and with fibrosis (N = 290).
Six alleles were identified and the MICA010 allele had the highest frequency in both groups. The MICA00201-02 allele was a protective factor for fibrosis (OR= 0.508, 95%CI= 0.34-0.76, Pc <0.05), while the MICA019 allele was suggested to be a risk allele for fibrosis (OR=1.95, 95%CI=1.25-3.03, Pc<0.005). In addition, two motifs, glycine (G) at position 14 and glutamine (Q) at position 251, were negatively associated with fibrosis (G14: OR=0.508, 95%CI=0.34-0.76, Pc <0.05 and Q251: OR=0.586, 95%CI=0.41-0.84, Pc <0.05). Moreover, the distribution of the MICA-129 genotype also showed the protective genotype (Pc<0.05, OR=0.319, 95%CI= 0.12-0.54) for fibrosis. The MICA00201-02 allele encoded all these motifs, and this suggested that it might lead to strong NK cell activation to kill HSCs, subsequently preventing fibrosis formation.
This study described initial evidence suggesting that the polymorphism of the MICA gene might be a marker for OV-derived periductal fibrosis.
慢性华支睾吸虫（OV）感染是导致进行性胆管周围纤维化（APF）进而引发胆管癌（CCA）的原因。自然杀伤（NK）细胞可通过自然杀伤细胞组 2 成员 D（NKG2D）受体与其在肝星状细胞（HSCs）上的配体之间的相互作用杀死 HSCs，这是纤维化形成的起始细胞。这可以抑制纤维化的形成。主要组织相容性复合体 I 类链相关蛋白 A（MICA）是 NKG2D 受体的配体，具有高度多态性的特征，参与 NKG2D 结合和 NK 细胞激活。本研究旨在探讨 OV 诱导的纤维化中 MICA 的多态性。
采用聚合酶链反应-序列特异性引物（PCR-SSP）和测序法对两组人群进行 MICA 分型：无纤维化的 OV 感染（N=99）和纤维化（N=290）。
鉴定出 6 个等位基因，两组人群中 MICA010 等位基因频率最高。MICA00201-02 等位基因是纤维化的保护因素（OR=0.508，95%CI=0.34-0.76，Pc<0.05），而 MICA019 等位基因提示为纤维化的风险等位基因（OR=1.95，95%CI=1.25-3.03，Pc<0.005）。此外，位置 14 的甘氨酸（G）和位置 251 的谷氨酰胺（Q）两个基序与纤维化呈负相关（G14：OR=0.508，95%CI=0.34-0.76，Pc<0.05 和 Q251：OR=0.586，95%CI=0.41-0.84，Pc<0.05）。此外，MICA-129 基因型的分布也显示出对纤维化的保护基因型（Pc<0.05，OR=0.319，95%CI=0.12-0.54）。MICA00201-02 等位基因编码所有这些基序，这表明它可能导致强烈的 NK 细胞激活，杀死 HSCs，从而防止纤维化的形成。
本研究初步表明，MICA 基因的多态性可能是 OV 胆管周围纤维化的标志物。
