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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
通路突变累积扰动评分：晚期胃癌免疫治疗的预后与预测生物标志物
英文原题：Pathway Mutation Accumulate Perturbation Score: A prognostic and predictive biomarker for immunotherapy in advanced gastric cancer.
查看英文原题
Pathway Mutation Accumulate Perturbation Score: A prognostic and predictive biomarker for immunotherapy in advanced gastric cancer.
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研究概要
基于 PMAPscore 的风险模型是预测晚期胃癌患者生存及免疫治疗反应的稳健工具，支持其在治疗分层中的临床应用。
研究思路结论见上方概要
背景
胃癌（GC）仍具有高度致命性，可用生物标志物有限。通路突变累积扰动评分（PMAPscore）利用通路水平突变，为预测免疫治疗反应和生存结局提供了新方法。
目的
旨在评估PMAPscore在接受免疫治疗的晚期胃癌（GC）患者中的预后和预测价值。
方法
分析了三组接受免疫治疗的胃癌（GC）患者队列：PUCH（北京大学肿瘤医院；n = 39，训练队列）、MSK（纪念斯隆凯特琳癌症中心；n = 19，验证队列）和SMC（三星医疗中心；n = 43，验证队列）。基于PMAPscore的风险模型被开发并验证用于生存结局。利用癌症基因组图谱（TCGA）胃癌数据（n = 431）探索了高风险和低风险组中的免疫机制。
结果
PMAPscore模型识别的低风险患者表现出显著更优的无进展生存期（PFS）、总生存期（OS）和持久临床获益（DCB）。在PUCH队列中，低风险患者的DCB率更高（85.7%对44.0%，p = 0.02），PFS更长（p < 0.001），OS也更长（p < 0.001）。在MSK和SMC队列中观察到相似趋势。多变量分析证实，低风险状态是改善PFS和OS的独立预测因子，优于肿瘤突变负荷（TMB）、程序性死亡配体1（PD-L1）表达、微卫星不稳定性（MSI）状态和胃肠免疫预后特征（GIPS）。TCGA数据表明，低风险肿瘤中抗肿瘤免疫活性增强，人类白细胞抗原（HLA）相关基因表达增加，B细胞和自然杀伤（NK）细胞浸润增多。
展开英文摘要原文
BACKGROUND
Gastric cancer (GC) remains highly lethal, with limited available biomarkers. The Pathway Mutation Accumulation Perturbation Score (PMAPscore), which leverages pathway-level mutations, provides a novel approach to predicting immunotherapy response and survival outcomes.
OBJECTIVES
To evaluate the prognostic and predictive value of the PMAPscore in patients with advanced GC undergoing immunotherapy. MATERIAL AND METHODS: Three cohorts of patients with GC treated with immunotherapy were analyzed: PUCH (Peking University Cancer Hospital; n = 39, training cohort), MSK (Memorial Sloan Kettering; n = 19, validation cohort) and SMC (Samsung Medical Center; n = 43, validation cohort). A PMAPscore-based risk model was developed and validated for survival outcomes. Immune mechanisms in highand low-risk groups were explored using The Cancer Genome Atlas (TCGA) GC data (n = 431).
RESULTS
Low-risk patients identified by the PMAPscore model exhibited significantly better progression-free survival (PFS), overall survival (OS) and durable clinical benefit (DCB). In the PUCH cohort, low-risk patients had higher DCB rates (85.7% vs 44.0%, p = 0.02), longer PFS (p < 0.001), and longer OS (p < 0.001). Similar trends were observed in the MSK and SMC cohorts. Multivariate analysis confirmed low-risk status as an independent predictor of improved PFS and OS, outperforming tumor mutation burden (TMB), programmed death-ligand 1 (PD-L1) expression, microsatellite instability (MSI) status, and the gastrointestinal immune prognostic signature (GIPS). The TCGA data indicated enhanced antitumor immune activity in low-risk tumors, with increased human leukocyte antigen (HLA)-related gene expression and greater B-cell and natural killer (NK) cell infiltration.
CONCLUSIONS
The PMAPscore-based risk model is a robust tool for predicting survival and immunotherapy responses in patients with advanced GC, supporting its clinical application for treatment stratification.
论文信息
- 作者
- Zhang Z、Yang G、Xing Y、Gao Y、Lu H
- 第一作者单位
- Institute of Stomatology, Baotou Medical College, China.China
- 通讯作者单位
- Institute of Medical Technology and Anesthesiology, Baotou Medical College, China.China
- 期刊
- Advances in clinical and experimental medicine : official organ Wroclaw Medical University2026 Apr
- 原文标识
- PubMed 41837463 · DOI 10.17219/acem/206937