RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Multi-Task Deep Learning on MRI for Tumor Segmentation and Treatment Response Prediction in an Experimental Model of Hepatocellular Carcinoma.
Multi-Task Deep Learning on MRI for Tumor Segmentation and Treatment Response Prediction in an Experimental Model of Hepatocellular Carcinoma.
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评估肝细胞癌(HCC)联合治疗的疗效,既需要准确的肿瘤勾画,也需要经过生物学验证的治疗反应预测。传统的基于MRI的标准主要依赖肿瘤大小,常因肿瘤异质性和假性进展而无法捕捉治疗疗效。本研究旨在开发并在生物学上验证一种多任务深度学习模型,该模型可在临床前大鼠模型中使用临床相关的多参数MRI同时分割HCC肿瘤并预测治疗结果。
在分配至对照组、索拉非尼组、NK细胞免疫治疗组和联合治疗组的大鼠中诱导原位HCC肿瘤。每周进行多参数MRI(T1w、T2w和对比增强MRI)扫描。我们开发了一种U-Net++架构,结合预训练的EfficientNet-B0编码器,可同时实现分割和分类任务。通过Dice系数和受试者工作特征曲线下面积(AUROC)评分评估模型性能,并通过组织学验证(H&E评估活力,TUNEL评估凋亡)使用线性回归分析评估生物学相关性。
多任务模型实现了精确的肿瘤分割(Dice系数 = 0.92,交并比(IoU)= 0.86),并可靠预测了治疗结果(AUROC = 0.97,准确率 = 85.0%)。MRI衍生的深度学习生物标志物与肿瘤活力和凋亡的组织学标志物强相关(均方根误差(RMSE):活力 = 0.1069,凋亡 = 0.013),表明该模型捕捉到了与治疗诱导的组织学变化相关的生物学相关影像特征。
这一多任务深度学习框架经组织学验证,证明了利用广泛可用的临床MRI序列对HCC治疗反应进行无创监测的可行性。通过将影像特征与潜在的肿瘤生物学联系起来,该模型突显了一条转化路径,有助于形成更具临床适用性的治疗疗效评估策略。
Background : Assessing the efficacy of combination therapies in hepatocellular carcinoma (HCC) requires both accurate tumor delineation and biologically validated prediction of therapeutic response. Conventional MRI-based criteria, which rely primarily on tumor size, often fail to capture treatment efficacy due to tumor heterogeneity and pseudo-progression.
This study aimed to develop and biologically validate a multi-task deep learning model that simultaneously segments HCC tumors and predicts treatment outcomes using clinically relevant multi-parametric MRI in a preclinical rat model. Methods : Orthotopic HCC tumors were induced in rats assigned to Control, Sorafenib, NK cell immunotherapy, and combination treatment groups. Multi-parametric MRI (T1w, T2w, and contrast enhanced MRI) scans were performed weekly.
We developed a U-Net++ architecture incorporating a pre-trained EfficientNet-B0 encoder, enabling simultaneous segmentation and classification tasks. Model performance was evaluated through Dice coefficients and area under the receiver operator characteristic curve (AUROC) scores, and histological validation (H&E for viability, TUNEL for apoptosis) assessed biological correlations using linear regression analysis. Results : The multi-task model achieved precise tumor segmentation (Dice coefficient = 0. 92, intersection over union (IoU) = 0. 86) and reliably predicted therapeutic outcomes (AUROC = 0. 97, accuracy = 85. 0%).
MRI-derived deep learning biomarkers correlated strongly with histological markers of tumor viability and apoptosis (root mean squared error (RMSE): viability = 0. 1069, apoptosis = 0. 013), demonstrating that the model captures biologically relevant imaging features associated with treatment-induced histological changes.
Conclusions : This multi-task deep learning framework, validated against histology, demonstrates the feasibility of leveraging widely available clinical MRI sequences for non-invasive monitoring of therapeutic response in HCC. By linking imaging features with underlying tumor biology, the model highlights a translational pathway toward more clinically applicable strategies for evaluating treatment efficacy.
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