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

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

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残余胃癌中肿瘤浸润淋巴细胞与程序性细胞死亡配体1表达相关的预后意义
目的:残胃癌(RGC)预后较差。由于它们不常见且异质性很大,因此需要新的预后和可靠的决定因素来预测RGC患者的临床病程。本研究旨在研究肿瘤浸润淋巴细胞(TILs)和程序性细胞死亡配体1 (PD-L1)状态作为RGC患者预后的生物标志物,以建立免疫相关评分。方法:对行根治性胃切除术的胃癌患者进行回顾性分析。组织学诊断为胃腺癌的RGC切除术纳入研究。采用二元logistic回归分析建立基于免疫参数的风险评分。根据RGCs免疫评分分为高危组(HR)、中危组(IR)和低危组(LR)。选择标志物(CD3+, CD4+/CD8+ T细胞和PD-L1)以评估其潜在的预后和治疗价值,并通过免疫组织化学(IHC)进行评估。结果:共有42例RGC患者入组研究。基于免疫参数的评分准确率为79%[受试者工作特征曲线下面积(AUC)=0.79, 95%可信区间(95% CI), 0.63-0.94, P=0.002],并将人群分为3个预后组:LR组10例(23.8%),IR组15例(35.7%),HR组17例(40.5%)。三组患者的临床病理及手术特点均无差异。在生存分析中,与LR组相比,HR组和IR组的无病生存率和总生存率更差。在多因素分析中,淋巴结转移和免疫评分危险组是与生存率差相关的独立因素。结论:使用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,肿瘤浸润性免疫淋巴细胞和PD-L1状态可能作为RGC患者潜在的预后生物标志物。
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