Evaluation of HLA-E Expression Combined with Natural Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer
Evaluation of HLA-E Expression Combined with Natural Killer Cell Status as a Prognostic Factor for Advanced Gastric Cancer
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DOI：
10.1245/s10434-022-11665-3
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发表时间：
2022-04-12
影响因子：
3.7
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
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作者：
Morinaga, Takeshi;Iwatsuki, Masaaki;Baba, Hideo
背景资料。NKG2A/HLA-E通路作为免疫检查点发挥作用，有可能利用治疗性抗体进行抑制。通过这一途径，免疫细胞失去活性，从而使癌症得以发展。我们的目的是确定人类白细胞抗原E的表达和NK细胞状态是否可以作为判断胃癌(GC)预后的生物标志物。我们纳入232例接受根治性胃切除的晚期胃癌患者，采用免疫组织化学方法检测人类白细胞抗原E的整体表达，并通过CD56和CD3的表达来识别NK细胞。采用生存分析的方法评价人类白细胞抗原-E的表达和NK细胞状态的意义。HLAE阳性患者104例(41.3%)，其无复发生存(RFS)预后明显低于HLAE阴性患者。此外，与NK高状态患者相比，NK低状态患者的RFS预后更差。多因素分析显示，HLAE表达是预后不良的独立危险因素(HR1.57，95%CI1.04~2.36，P=0.031)。此外，低NK状态的HLAE阳性患者的RFS最短，尤其是在上GC组。人类白细胞抗原E是胃癌根治性切除后的预后因素，而人类白细胞抗原E的表达和NK状态是预测晚期胃癌预后的敏感生物标志物。
Background. The NKG2A/HLA-E pathway functions as an immune checkpoint with potential for inhibition using therapeutic antibodies. Through this pathway, immune cells lose activity, which allows cancers to progress. We aimed to determine whether HLA-E expression combined with NK cell status serves as a prognostic biomarker for gastric cancer (GC).Methods. We enrolled patients (n = 232) with advanced GC who underwent curative gastrectomy Immunohistochemical analyses of global HLA-E expression, and the expression of CD56 and CD3 to identify NK cells were performed. Survival analysis was performed to evaluate the significance of HLA-E expression and NK status.Results . Patients with HLA-E-positive was 104 (41.3%) and had significantly worse prognosis of relapse-free survival (RFS) compared with those with HLA-E-negative. Moreover, patients with NK Low status had worse prognoses for RFS compared with those with NK High status. Statistical analysis of RFS demonstrated that HLA-E expression was a significant independent factor for poor prognosis (HR 1.57, 95% CI 1.04-2.36, P = 0.031). Furthermore, HLA-E-positive patients with low NK low status experienced the shortest RFS, particularly those in the upper GC group.Conclusions. HLA-E served as a prognostic factor after curative resection of GC, and HLA-E expression combined with NK status served as a sensitive prognostic biomarker for advanced GC.