| 杨龙龙,尹清臣,李忠信,等.进展期食管胃结合部腺癌患者术后辅助腹腔热灌注化疗的蛋白表达及免疫细胞变化分析[J].肿瘤学杂志,2024,30(2):99-110. |
| 进展期食管胃结合部腺癌患者术后辅助腹腔热灌注化疗的蛋白表达及免疫细胞变化分析 |
| An Analysis of Protein Expression and Immune Cell Levels in Patients with Advanced Adenocarcinoma of Esophagogastric Junction Receiving Postoperative Hyperthermic Intraperitoneal Chemotherapy |
| 投稿时间：2023-09-08 |
| DOI：10.11735/j.issn.1671-170X.2024.02.B003 |
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| 中文关键词: 胃食管结合部腺癌 腹腔热灌注化疗 己糖激酶结构域蛋白1 膜联蛋白A13 免疫细胞 |
| 英文关键词:adenocarcinoma of esophagogastric junction hyperthermic intraperitoneal chemotherapy hexokinase domain-containing protein 1 annexin A13 immune cells |
| 基金项目:河北省重点研发计划自筹项目（182777241） |
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| 中文摘要: |
| 摘 要： ［目的］ 分析进展期食管胃结合部腺癌（adenocarcinoma of esophagogastric junction，AEG）术后辅助腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy，HIPEC）治疗患者的免疫细胞水平及癌组织中己糖激酶结构域蛋白1（hexokinase domain-containing protein 1，HKDC1）、膜联蛋白A13（annexin A13，ANXA13）的表达，探讨两者对AEG患者预后的影响。［方法］ 基于GSE74553、GSE96668、GSE147762数据集差异基因的筛选，选取2018年6月至2019年6月邯郸市中心医院进展期AEG术后辅助HIPEC患者37例。采用免疫组化法检测AEG组织和癌旁组织中HKDC1、ANXA13的表达，采用转录组测序技术检测HIPEC后患者血液中免疫细胞的水平，分析免疫细胞与HKDC1、ANXA13的关系。［结果］GSE74553、GSE96668、GSE147762数据集的共有差异基因包括上调基因PGA5、MT1G和下调基因HKDC1、ANXA13、MUC13。经多种数据库及临床数据验证，HKDC1、ANXA13基因在食管癌、胃癌、AEG组织中表达明显高于癌旁组织（P均＜0.05）。随访截至2022年10月31日，37例患者总生存率为27.0%，中位生存时间为31个月。HKDC1、ANXA13的阳性表达率分别为62.2%、51.4%，两者阳性表达者的总生存率均显著短于阴性表达者（21.7% vs 35.7%，10.5% vs 44.4%）；HKDC1、ANXA13阳性和阴性表达者的中位生存时间差异均有统计学意义（30个月vs 38个月，P=0.040；19 个月vs 37个月，P=0.001）。共检测出22种免疫细胞，与HKDC1阴性表达者相比，CD8+ T细胞、效应NK细胞在HKDC1阳性组显著降低（P=0.020、0.010），M2型巨噬细胞显著升高（0.05±0.04 vs 0.09±0.04，P=0.018）。效应NK细胞、调节T细胞（Tregs）在ANXA13阳性和阴性组差异有统计学意义（P=0.040、0.020）。［结论］HIPEC辅助治疗可能参与免疫细胞的调控，M2型巨噬细胞水平与HKDC1表达相关，Tregs水平与ANXA13表达相关，HKDC1、ANXA13阳性表达可能是导致AEG患者治疗后预后差的危险因素。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate the immune cell levels and the expression of hexokinase domain- containing protein 1 (HKDC1) and annexin A13 (ANXA13) in cancer tissue of patients with advanced adenocarcinoma of esophagogastric junction (AEG) treated with adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) after surgery， and their relation with the prognosis of patients. ［Methods］ Thirty seven patients with advanced AEG who received postoperative HIPEC in Handan Central Hospital from June 2018 to June 2019 were enrolled. The expression of HKDC1， ANXA13 in cancer tissues and pericancerous tissues was detected by immunohistochemistry， the levels of peripheral immune cells in patients after HIPEC was examined by transcriptome sequencing technique. The relationship of HKDC1 and ANXA13 expression with immune cells level and prognosis of patients was analyzed. ［Results］ The common differentially expressed genes in the GSE74553， GSE96668， and GSE147762 datasets include up-regulated genes PGA5， MT1G， and down-regulated genes HKDC1， ANXA13 and MUC13. Verified by multiple databases and clinical data， the expression of HKDC1 and ANXA13 genes in esophageal cancer， gastric cancer， and AEG tissues were significantly higher than those in normal tissues (all P<0.05). The deadline for follow-up is October 31， 2022， the overall survival rate of 37 patients was 27.0%， with a median survival time of 31 months. The positive expression rates of HKDC1 and ANXA13 in AEG tissues were 62.2% and 51.4%， respectively. The overall survival rate in AEG patients with positive HKDC1 and ANXA13 expression was significantly lower than that in patients with negative expression (21.7% vs 35.7%， 10.5% vs 44.4%). The median survival time in patients with positive HKDC1 and ANXA13 was shorter than that in patients with negative expression (30 months vs 38 months， P=0.040； 19 months vs 37 months， P=0.001). Compared with HKDC1 negative patients， CD8+ T cells and NK cells activated were significantly decreased in the HKDC1 positive patients(P=0.020， 0.010)， while macrophages M2 was increased (0.05±0.04 vs 0.09±0.04， P=0.018). There was a statistically significant difference in NK cells activated and regulatory T cells (Tregs) between patients with positive ANXA13 expression and negative expression (P=0.040， P=0.020). ［Conclusion］ The study indicates that macrophage M2 level is associated with HKDC1 expression， Tregs levels is associated with ANXA13 expression， and positive expression of HKDC1 and ANXA13 may be associated with poor prognosis in AEG patients after adjuvant HIPEC therapy. |
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