摘要： 目的 探讨食管癌患者外周血中白细胞介素（IL）-1β和组织中程序性死亡分子1（PD-1）的表达情况及其对患者临床病理特征和预后的影响。方法 选取2018年1月至2020年5月于河南科技大学第一附属医院接受手术治疗的食管癌患者127例，根据术后3年患者的存活情况，将患者分为存活组（n=95）和死亡组（n=32）。收集患者临床资料，免疫组织化学检测食管癌组织中PD-1、程序性死亡配体1（PD-L1）的表达，酶联免疫吸附试验（ELISA）检测外周血中IL-6、IL-1β和肿瘤坏死因子-α（TNF-α）的水平。Cox回归分析影响患者术后3年死亡的危险因素。绘制IL-1β、PD-1不同表达患者的3年Kaplan-Meier生存曲线，log-rank检验比较3组的生存率。结果 死亡组年龄≥60岁、淋巴结转移、浸润至肌层、肿瘤直径> 3 cm、IL-1β高水平、TNF-α高水平和PD-1阳性表达患者比例均高于生存组，IL-6高水平患者比例低于生存组，组间比较均有统计学差异（P < 0.05）。浸润至肌层、肿瘤直径> 3 cm、IL-1β高水平和PD-1阳性表达为影响患者术后死亡的独立危险因素。IL-1β正常水平+PD-1阴性组、IL-1β高水平+PD-1阳性组和IL-1β正常水平+PD-1阳性组/IL-1β高水平+PD-1阴性组患者的3年生存率分别为92.4%、13.3%和84.2%，组间比较有统计学差异（χ²=82.318，P < 0.01），且IL-1β高水平+PD-1阳性组患者生存率最低。结论 PD-1阳性表达和IL-1β高水平为影响食管癌患者死亡的独立危险因素，且PD-1阳性表达+IL-1β高水平患者的生存率低。

食管癌患者外周血中白细胞介素-1β和组织中程序性死亡分子1的表达对预后的影响及临床意义

王献¹, 尚自强¹, 杨冬², 杨惠³

1. 河南科技大学第一附属医院, 河南科技大学临床医学院胸外科, 河南 洛阳 471003;
2. 河南省人民医院, 郑州大学人民医院胸外科, 郑州 450003;
3. 河南省人民医院, 郑州大学人民医院消化内科, 郑州 450003

收稿日期:2022-12-13出版日期:2023-12-30发布日期:2023-12-12
通讯作者:王献E-mail:zhufansha952@163.com
作者简介:王献(1982-),男,副主任医师,硕士
基金资助:河南省医学科技攻关计划联合共建立项项目（LHGJ20200023）


关键词: 食管癌, 肿瘤微环境, 白细胞介素-1β, 程序性死亡1受体
Abstract: Objective To detect the expressions of interleukin-1β (IL-1β) in peripheral blood and programmed death molecule 1 (PD-1) in esophageal cancer tissues and to analyze their influence on clinicopathological features and prognosis of patients.Methods A total of 127 patients with esophageal cancer who underwent surgical treatment at the First Affiliated Hospital of Henan University of Science and Technology from January 2018 to May 2020 were collected and divided into two groups:the survival group (n=95) and the death group (n=32), based on their survival status 3 years after surgery. Clinical data of the patients were collected. The expressions of PD-1 and programmed death ligand 1 (PD-L1) in esophageal cancer tissues were detected through immunohistochemistry, while the levels of IL-6, IL-1β, and tumor necrosis factor-α (TNF-α) in peripheral blood were measured using enzyme-linked immunosorbent assay (ELISA). Cox regression analysis was performed to identify the risk factors for death 3 years after surgery. The 3-year Kaplan-Meier survival curves of patients with different expressions of IL-1β and PD-1 were plotted, and the survival rates among the three groups were compared using the log-rank test.Results In the death group, the proportions of patients with age ≥ 60 years old, lymph node metastasis, infiltration into the muscle layer, tumor diameter > 3 cm, IL-1β high level, TNF-α high level, and PD-1 positive expression were higher than those in the survival group. Conversely, the proportions of patients with high IL-6 levels were lower than those in the survival group, with statistically significant differences between the groups (P < 0.05). Infiltration into the myometrium, tumor diameter > 3 cm, high IL-1β level, and PD-1 positive expression were identified as independent risk factors for postoperative death. The 3-year survival rates were 92.4%, 13.3%, and 84.2% for patients in the normal IL-1β +PD-1 negative group, high IL-1β +PD-1 positive group, and normal IL-1β +PD-1 positive group/high IL-1β +PD-1 negative group, respectively. Significant differences existed between the groups (χ²=82.318, P < 0.01), with the highest survival rate observed in the normal IL-1β + PD-1 negative group and the lowest in the high IL-1β + PD-1 positive group.Conclusion Positive expression of PD-1 and a high level of IL-1β were identified as independent risk factors for death in patients with esophageal cancer. Notably, patients with positive expression of PD-1 + high levels of IL-1β exhibited a low survival rate.
Key words: esophageal cancer, tumor microenvironment, interleukin-1β, programmed death 1 receptor
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