Kopp R, Glas J, Lau-Werner U, Albert E D, Weiss E H
Department of Surgery, Klinikum Grosshadern, University of Munich, Munich, Germany.
J Clin Immunol. 2009 Jul;29(4):545-54. doi: 10.1007/s10875-009-9288-6. Epub 2009 Apr 8.
The major histocompatibility complex class I related A (MICA) and MICB molecules are ligands of NKG2D receptors on natural killer cells, gamma/delta T cells, and CD8ass T cells that mediate host antitumor immune response. The role of MICA-TM and MICB C1_2_A alleles in patients with colorectal cancer has not yet been investigated.
We have analyzed the MICA-TM and MICB C1_2_A polymorphisms in colorectal cancer patients (n = 79) by polymerase chain reaction amplification, subsequent electrophoresis, and sequencing in comparison to a previously analyzed cohort of healthy controls (n = 306). Allele frequencies obtained for MICA-TM and MICB C1_2_A were compared to histopathological data regarding tumor invasion, disease progression, microsatellite instability, and the presence of KRAS mutations (codon 12) and analyzed for possible impact on tumor-related survival (n = 61).
Allele frequencies of MICA-TM and MICB C1_2_A polymorphisms were not different in patients with colorectal cancer in comparison to normal controls. In colorectal cancer patients, MICA-TM A4 allele was directly and MICA-TM A5 allele was inversely associated with lymph node involvement and advanced UICC stages. Tumor-related survival in colorectal cancer patients was significantly reduced in the presence of the MICA-TM A4 allele (p = 0.015). In patients with microsatellite stable tumors, survival was reduced in association with the MICA-TM A4 allele (p = 0.006) and MICA-TM A9 allele (p = 0.034), but increased in patients showing the MICA-TM A5 allele (p = 0.042).
Specific MICA-TM alleles seem to influence tumor progression and midterm survival of patients with colorectal cancer, indicating an important role of host innate immune predisposition involving NKG2D mediated antitumor response.
主要组织相容性复合体I类相关A（MICA）和MICB分子是自然杀伤细胞、γ/δT细胞以及CD8αβT细胞上NKG2D受体的配体，可介导宿主抗肿瘤免疫反应。MICA - TM和MICB C1_2_A等位基因在结直肠癌患者中的作用尚未得到研究。
我们通过聚合酶链反应扩增、随后的电泳和测序，分析了79例结直肠癌患者的MICA - TM和MICB C1_2_A多态性，并与之前分析的306例健康对照队列进行比较。将MICA - TM和MICB C1_2_A的等位基因频率与肿瘤浸润、疾病进展、微卫星不稳定性以及KRAS突变（密码子12）的组织病理学数据进行比较，并分析其对肿瘤相关生存（61例）的可能影响。
与正常对照相比，结直肠癌患者中MICA - TM和MICB C1_2_A多态性的等位基因频率没有差异。在结直肠癌患者中，MICA - TM A4等位基因与淋巴结受累和UICC晚期呈直接相关，而MICA - TM A5等位基因与之呈负相关。存在MICA - TM A4等位基因时，结直肠癌患者的肿瘤相关生存率显著降低（p = 0.015）。在微卫星稳定肿瘤患者中，MICA - TM A4等位基因（p = 0.006）和MICA - TM A9等位基因（p = 0.034）与生存率降低相关，但显示MICA - TM A5等位基因的患者生存率增加（p = 0.042）。
特定的MICA - TM等位基因似乎影响结直肠癌患者的肿瘤进展和中期生存，表明宿主先天免疫易感性在NKG2D介导的抗肿瘤反应中起重要作用。
