间皮素作为癌症免疫治疗的生物标志物和治疗靶点
Mesothelin as Biomarker and Therapeutic Target for Immunotherapy in Cancer.
癌症仍是一个关键的全球健康问题,原因在于发现晚、耐药和高死亡率。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Integration of the GRIm Score with Pathologic Immune and Stromal Markers to Develop a Combined Prognostic Model in Gastric Cancer: A Retrospective Single-Center Study.
Integration of the GRIm Score with Pathologic Immune and Stromal Markers to Develop a Combined Prognostic Model in Gastric Cancer: A Retrospective Single-Center Study.
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Gustave Roussy免疫评分(GRIm)反映全身炎症和营养状态,已成为多种恶性肿瘤中一种简单、可重复的预后生物标志物。然而,在胃癌中,其与肿瘤微环境因素之间的预后交互作用尚不明确。本研究首要目的是评估GRIm评分对可切除胃腺癌患者的预后价值;次要目的是确定将GRIm评分与肿瘤微环境相关病理标志物结合能否改善预后分层。
本回顾性研究分析了2007至2018年间在特拉基亚大学医学院接受治疗的188例可切除胃腺癌患者。根据术前乳酸脱氢酶(LDH)、白蛋白和中性粒细胞/淋巴细胞比值(NLR)计算GRIm评分。对手术标本评估病理参数,包括程序性死亡配体1(PD-L1)表达(联合阳性评分[CPS]≥1或<1)、肿瘤—间质比(TSR;间质成分≥50%或<50%)以及TIL密度(CD8⁺≥10%或<10%)。采用Kaplan-Meier和多变量Cox分析评估生存结局。
患者平均年龄61.8岁,以男性为主(72.3%)。GRIm评分低的患者无病生存期(DFS,24比12个月;P=0.004)和总生存期(OS,32比19个月;P=0.006)显著更长。多变量分析显示,GRIm评分仍是DFS(P=0.035)和OS(P=0.044)的独立预测因子。在联合模型中,GRIm-TSR分类的分层效果最显著(中位DFS=35比12个月;OS=45比19个月;P分别为0.014和0.001),且仍具有独立预后意义(风险比[HR]=1.23;P=0.005)。结合PD-L1和TIL密度也能改善预后判别。
GRIm评分是一种稳健且成本效益高的生物标志物,可独立预测可切除胃腺癌患者的DFS和OS。将其与PD-L1、TIL和TSR等微环境标志物结合,可捕捉肿瘤侵袭性的互补生物学维度,为个体化风险评估和术后管理提供综合且临床可行的框架。仍需前瞻性多中心验证。
Background and Objectives : The Gustave Roussy Immune (GRIm) score, reflecting systemic inflammation and nutritional status, has emerged as a simple and reproducible prognostic biomarker in various malignancies.
However, its prognostic interaction with tumor microenvironmental factors remains unclear in gastric cancer. The primary aim of this study was to evaluate the prognostic value of the GRIm score in patients with resectable gastric adenocarcinoma, while the secondary aim was to determine whether integrating the GRIm score with tumor microenvironment-related pathological markers could improve prognostic stratification. Materials and Methods : This retrospective study analyzed 188 patients with resectable gastric adenocarcinoma treated at the Trakya University Faculty of Medicine between 2007 and 2018. GRIm scores were calculated from preoperative lactate dehydrogenase (LDH), albumin, and neutrophil-to-lymphocyte ratio (NLR) values. Pathologic parameters, including programmed death-ligand 1 (PD-L1) expression (combined positive score [CPS] 1 vs. <1), tumor-stroma ratio (TSR; stromal component 50% vs. <50%), and tumor-infiltrating lymphocyte (TIL) density (CD8+ 10% vs. <10%), were evaluated on surgical specimens. Survival outcomes were assessed using Kaplan-Meier and multivariate Cox analyses. Results : The study population had a mean age of 61. 8 years and was predominantly male (72.
3%). Patients with low GRIm scores had significantly longer disease-free survival (DFS; 24 vs. 12 months; p = 0. 004) and overall survival (OS; 32 vs. 19 months; p = 0. 006). In multivariate analysis, the GRIm score remained an independent predictor for both disease-free survival ( p = 0. 035) and overall survival ( p = 0. 044). Among combined models, the GRIm-TSR classification provided the most pronounced stratification (median DFS = 35 vs. 12 months; OS = 45 vs. 19 months; p = 0. 014 and 0. 001, respectively), retaining independent prognostic significance (hazard ratio [HR] = 1.
23; p = 0. 005). Integrating GRIm with PD-L1 and TIL density also improved prognostic discrimination. Conclusions : The GRIm score is a robust and cost-effective biomarker that independently predicts disease-free survival and overall survival in resectable gastric adenocarcinoma.
Its combination with microenvironmental markers-PD-L1, TIL, and TSR-captures complementary biological dimensions of tumor aggressiveness, offering an integrative and clinically feasible framework for individualized risk assessment and postoperative management. Prospective multicenter validation is warranted.
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