Impact of "Killer Immunoglobulin-Like Receptor /Ligand" Genotypes on Outcome following Surgery among Patients with Colorectal Cancer: Activating KIRs Are Associated with Long-Term Disease Free Survival.
Impact of "Killer Immunoglobulin-Like Receptor /Ligand" Genotypes on Outcome following Surgery among Patients with Colorectal Cancer: Activating KIRs Are Associated with Long-Term Disease Free Survival.
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DOI：
10.1371/journal.pone.0132526
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Tirnaksiz MB
中科院分区：
文献类型：
--
作者：
Beksac K;Beksac M;Dalva K;Karaagaoglu E;Tirnaksiz MB
大约30%的II/III期结直肠癌患者在手术后复发。宿主免疫球蛋白样受体（KIR）基因型如何改变宿主介导的抗肿瘤细胞毒性的个体调节对于预测结果至关重要。我们分析了KIR和KIR配体人类白细胞抗原I类基因型的频率，以及它们对复发和无病生存期（DFS）的影响。在2005年至2008年期间随机选择的87例接受R 0切除手术的结直肠癌患者中，29例在中位5年随访期内癌症进展的患者与58例在同一时间段内没有复发的患者进行了比较。复发病例与非复发病例具有相似的肿瘤分期，但具有不同的定位。我们使用从病理档案淋巴和肿瘤组织中分离的DNA进行KIR和KIR配体（HLA-C，C1组，C2组和HLA-A-Bw 4）基因分型。在复发病例中，观察到KIR 2DL 1（抑制性KIR）和A-Bw 4（抑制性KIR 3DL 1的配体）的频率更高（p=0.017和p=0.024）;观察到KIR 2DS 2和KIR 2DS 3（均为激活性KIR）的频率较低（p=0.005和p=0.043）。类似地，在非复发组中，抑制性KIR-配体组合2DL 1-C2和2DL 3-C1的频率较低，而活化性组合2DS 2-C1的频率较高。缺乏KIR 2DL 1、2DL 1-C2和2DL 3-C1改善了无病生存期（DFS）（100% vs. 62.3%，p=0.05; 93.8% vs. 60.0%，p=0.035; 73.6% vs. 55.9%，p=0.07）。KIR 2DS 2、2DS 3和2DS 2-C1的存在改善了DFS（77.8% vs. 48.5%，p=0.01; 79.4% vs. 58.5%，p=0.003; 76.9% vs. 51.4%，p=0.023）。KIR 2DS 3降低了复发风险（HR=0.263，95% CI = 0.080-0.863，p=0.028）。激活KIR的数量与DFS密切相关，无/1/2个KIR：54/77/98个月（p=0.004）。总之，与肿瘤定位或分期无关的活化KIR数量增加和抑制KIR缺乏的遗传与长期DFS相关。
Approximately 30 % of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs) genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS). Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations. We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4) genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR) and A-Bw4 (ligand for inhibitory KIR3DL1) were observed more frequently (p=0.017 and p=0.024); and KIR2DS2 and KIR2DS3 (both activating KIRs) were observed less frequently (p=0.005 and p=0.043). Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS) (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07). The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023). KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI = 0.080-0.863, p=0.028). The number of activating KIRs are correlated strongly with DFS, none/ one/ two KIR : 54/77/98 months (p=0.004). In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs, independent of tumor localization or stage, is associated with long-term DFS.