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肿瘤浸润淋巴细胞与程序性细胞死亡配体1表达相关对残胃癌的预后影响

Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer.

作者信息

Pereira Marina Alessandra, Pertille Ramos Marcus Fernando Kodama, Dias André Roncon, Cardili Leonardo, de Moraes Rafael Dyer Rodrigues, Ribeiro Renan Ribeiro E, Alves Venancio Avancini Ferreira, Zilberstein Bruno, de Mello Evandro Sobroza, Jr Ulysses Ribeiro

机构信息

Department of Gastroenterology, Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo, (ICESP-HCFMUSP) São Paulo, SP 01246-000, Brazil.

Department of Pathology, Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo, (ICESP-HCFMUSP) São Paulo, SP 01246-000, Brazil.

出版信息

Chin J Cancer Res. 2022 Dec 30;34(6):612-622. doi: 10.21147/j.issn.1000-9604.2022.06.09.

Abstract

OBJECTIVE

Remnant gastric cancer (RGC) is usually associated with a worse prognosis. As they are less common and very heterogeneous tumors, new prognostic and reliable determinants are required to predict patients' clinical course for RGC. This study aimed to investigate the tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) status as prognostic biomarkers in a cohort of patients with RGC to develop an immune-related score.

METHODS

Patients with gastric cancer (GC) who underwent curative intent gastrectomy were retrospectively investigated. RGC resections with histological diagnosis of gastric adenocarcinoma were enrolled in the study. The risk score based on immune parameters was developed using binary logistic regression analysis. RGCs were divided into high-risk (HR), intermediate-risk (IR), and low-risk (LR) groups based on their immune score. The markers (CD3+, CD4+/CD8+ T cells and PD-L1) were selected for their potential prognostic, therapeutic value, and evaluated by immunohistochemistry (IHC).

RESULTS

A total of 42 patients with RGC were enrolled in the study. The score based on immune parameters exhibited an accuracy of 79% [the area under the receiver operating characteristic curve (AUC)=0.79, 95% confidence interval (95% CI), 0.63-0.94, P=0.002], and the population was divided into 3 prognostic groups: 10 (23.8%) patients were classified as LR, 15 (35.7%) as IR, and 17 (40.5%) as HR groups. There were no differences in clinicopathological and surgical characteristics between the three groups. In survival analysis, HR and IR groups had worse disease-free survival and overall survival rates compared to the LR group. In the multivariate analysis, lymph node metastasis and the immune score risk groups were independent factors related to worse survival.

CONCLUSIONS

A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with survival. Accordingly, tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic biomarker for patients with RGC.

摘要

目的

残胃癌(RGC)通常预后较差。由于它们是较少见且非常异质性的肿瘤,需要新的预后性且可靠的决定因素来预测RGC患者的临床病程。本研究旨在调查肿瘤浸润淋巴细胞(TILs)和程序性细胞死亡配体1(PD-L1)状态作为RGC患者队列中的预后生物标志物,以建立一个免疫相关评分。

方法

对接受根治性胃切除术的胃癌(GC)患者进行回顾性研究。组织学诊断为胃腺癌的RGC切除术患者纳入本研究。使用二元逻辑回归分析建立基于免疫参数的风险评分。根据免疫评分将RGC分为高风险(HR)、中风险(IR)和低风险(LR)组。选择标志物(CD3 +、CD4 + / CD8 + T细胞和PD-L1)是因其潜在的预后、治疗价值,并通过免疫组织化学(IHC)进行评估。

结果

本研究共纳入42例RGC患者。基于免疫参数的评分显示准确率为79% [受试者工作特征曲线(AUC)下面积 = 0.79,95%置信区间(95% CI),0.63 - 0.94,P = 0.002],并且该人群被分为3个预后组:10例(23.8%)患者被归类为LR组,15例(35.7%)为IR组,17例(40.5%)为HR组。三组之间的临床病理和手术特征无差异。在生存分析中,HR组和IR组与LR组相比,无病生存率和总生存率更差。在多变量分析中,淋巴结转移和免疫评分风险组是与较差生存相关的独立因素。

结论

具有免疫相关标志物的评分系统能够区分与生存相关的RGC预后组。因此,肿瘤浸润免疫淋巴细胞和PD-L1状态可能作为RGC患者的潜在预后生物标志物。

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