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吲哚胺2,3-双加氧酶1(IDO1)表达和CD8 + T细胞水平是新辅助化疗前胃癌术前标本中有用的预后生物标志物。

IDO1 Expression and CD8+ T-Cell Levels Are Useful Prognostic Biomarkers in Preoperative Gastric Cancer Specimens Before Neoadjuvant Chemotherapy.

作者信息

Chen Hu, Zheng QiaoLin, Jiang Yiting, Lin Lin, Yang Yinghong

机构信息

Department of Pathology, Fujian Medical University Union Hospital.

Gastrointestinal Cancer Institute, Fujian Medical University, Fuzhou, China.

出版信息

Appl Immunohistochem Mol Morphol. 2025 Jan 1;33(1):1-9. doi: 10.1097/PAI.0000000000001238. Epub 2024 Nov 14.

Abstract

The tumor immune microenvironment occupies an important position in gastric cancer. In this study, we investigated the relationship between indoleamine 2,3-dioxygenase 1 (IDO1), programmed cell death 1 ligand (PD-L1) expressioon, and CD8+ T-cell levels and their efficacy and prognostic value in preoperative gastric cancer specimens before neoadjuvant chemotherapy (NAC). A total of 162 patients with locally advanced gastric cancer were collected in this study. IDO1, PD-L1 expression, and CD8+ T-cell levels in the biopsy samples was detected by immunohistochemical staining, and the relationship between these indexes and the patients' clinicopathological parameters, chemotherapeutic efficacy, and prognosis were investigated. The IDO1 positivity rate was 43.2%. High expression of IDO1 was significantly associated with poor chemotherapeutic efficacy, lymph node metastasis (P<0.05). The PD-L1 positivity rate (using the combined positive score) was 38.2%, and was not related to any clinicopathological variable. Higher CD8+ T-cell levels were associated with a lower rate of lymph node metastasis and lower ypTNM stage (P<0.05). Higher CD8+ T-cell levels were negatively correlated with IDO1 expression (r=-0.224, P<0.05) and positively correlated with PD-L1 expression (r=0.254, P<0.05). Cox regression analysis demonstrated that higher CD8+ T-cell levels was an independent risk factor for overall survival (OS) and the expression of IDO1 had a significantly poorer disease-free survival (DFS). Overexpression of IDO1 and lower CD8+ T-cell levels were associated with poor survival in patients with gastric cancer who received neoadjuvant chemotherapy, and overexpression of IDO1 were associated with the poor tumor response. Our data suggest that IDO1 and CD8 testing of biopsy specimens might be a simple and effective prognostic biomarker for gastric cancer, and IDO1 could predict efficacy of neoadjuvant chemotherapy in gastric cancer.

摘要

肿瘤免疫微环境在胃癌中占据重要地位。在本研究中,我们调查了吲哚胺2,3-双加氧酶1(IDO1)、程序性细胞死亡1配体(PD-L1)表达、CD8 + T细胞水平之间的关系,以及它们在新辅助化疗(NAC)前的术前胃癌标本中的疗效和预后价值。本研究共收集了162例局部晚期胃癌患者。通过免疫组织化学染色检测活检样本中的IDO1、PD-L1表达和CD8 + T细胞水平,并研究这些指标与患者临床病理参数、化疗疗效和预后之间的关系。IDO1阳性率为43.2%。IDO1高表达与化疗疗效差、淋巴结转移显著相关(P<0.05)。PD-L1阳性率(采用联合阳性评分)为38.2%,与任何临床病理变量均无关。较高的CD8 + T细胞水平与较低的淋巴结转移率和较低的ypTNM分期相关(P<0.05)。较高的CD8 + T细胞水平与IDO1表达呈负相关(r=-0.224,P<0.05),与PD-L1表达呈正相关(r=0.254,P<0.05)。Cox回归分析表明,较高的CD8 + T细胞水平是总生存期(OS)的独立危险因素,IDO1的表达与无病生存期(DFS)显著较差相关。IDO1过表达和较低的CD8 + T细胞水平与接受新辅助化疗的胃癌患者生存率低相关,IDO1过表达与肿瘤反应差相关。我们的数据表明,活检标本的IDO1和CD8检测可能是一种简单有效的胃癌预后生物标志物,IDO1可以预测胃癌新辅助化疗的疗效。

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