免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Machine learning models demonstrate that clinicopathologic variables are comparable to gene expression prognostic signature in predicting survival in uveal melanoma.
Machine learning models demonstrate that clinicopathologic variables are comparable to gene expression prognostic signature in predicting survival in uveal melanoma.
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我们的研究表明,与不易获取的 GEPS 相比,常规组织学和临床变量足以用于患者风险分层。
由于并非所有葡萄膜黑色素瘤患者都能进行分子检测,我们旨在利用基于常规组织学和临床变量的机器学习模型,识别具有成本效益的预后工具以进行风险分层。
我们在一个由164例未经先前治疗的164名患者的眼球摘除原发性葡萄膜黑色素瘤组成的发现队列中,确定了重要的预后参数。随后,我们利用来自癌症基因组图谱数据库中80例具有可用基因表达预后特征(GEPS)的葡萄膜黑色素瘤,验证了发现队列中识别出的最重要参数的预后预测能力。使用受试者工作特征曲线(ROC),将三种不同的生存分析模型(Cox比例风险(CPH)、随机生存森林(RSF)和生存梯度提升(SGB))的性能与GEPS进行了比较。
在三种选择方法中,BAP1状态、核仁大小、年龄、每1 mm²有丝分裂率以及睫状体浸润均被确定为显著的OS预测因子;BAP1状态、核仁大小、最大基底肿瘤直径、TIL(肿瘤浸润淋巴细胞)密度以及肿瘤相关巨噬细胞密度被确定为显著的PFS预测因子。中位生存时间点的ROC曲线显示,SGB研究所选模型中的显著参数在预测OS方面优于GEPS。对于PFS,SGB模型的表现与GEPS相似。时间依赖性AUC显示,SGB模型在预测OS和转移风险方面优于GEPS。
Since molecular assays are not accessible to all uveal melanoma patients, we aim to identify cost-effective prognostic tool in risk stratification using machine learning models based on routine histologic and clinical variables. EXPERIMENTAL DESIGN: We identified important prognostic parameters in a discovery cohort of 164 enucleated primary uveal melanomas from 164 patients without prior therapies. We then validated the prognostic prediction of top important parameters identified in the discovery cohort using 80 uveal melanomas from the Tumor Cancer Genome Atlas database with available gene expression prognostic signature (GEPS). The performance of three different survival analysis models (Cox proportional hazards (CPH), random survival forest (RSF), and survival gradient boosting (SGB)) was compared against GEPS using receiver operating curves (ROC).
In all three selection methods, BAP1 status, nucleoli size, age, mitotic rate per 1 mm 2 , and ciliary body infiltration were identified as significant overall survival (OS) predictors; and BAP1 status, nucleoli size, largest basal tumor diameter, tumor-infiltrating lymphocyte density, and tumor-associated macrophage density were identified as significant progression-free survival (PFS) predictors. ROC plots for the median survival time point showed that significant parameters in SGB studied model can predict OS better than GEPS. For PFS, SGB model performed similarly to GEPS. The time-dependent area under the curve (AUC) showed SGB model performing better than GEPS in predicting OS and metastatic risk.
Our study shows that routine histologic and clinical variables are adequate for patient risk stratification in comparison with not readily accessible GEPS.
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