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:A multi-class classification algorithm based on hematoxylin-eosin staining for neoadjuvant therapy in rectal cancer: a retrospective study.
A multi-class classification algorithm based on hematoxylin-eosin staining for neoadjuvant therapy in rectal cancer: a retrospective study.
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新辅助治疗(NAT)是局部晚期直肠癌的主要治疗选择。随着机器/深度学习算法的最新进展,利用放射学和/或病理学图像预测NAT的治疗反应已成为可能。
然而,迄今为止报道的程序仅限于二分类,只能区分病理完全缓解(pCR)。在临床实践中,病理NAT反应分为四类:TRG0-3,其中0为pCR,1为中度反应,2为轻微反应,3为不良反应。
因此,实际临床中对风险分层的需求仍未得到满足。通过使用ResNet(残差神经网络),我们开发了一种基于苏木精-伊红(HE)图像的多分类器,将反应分为三组(TRG0、TRG1/2和TRG3)。
总体而言,该模型在40×放大倍数下达到AUC 0.97,在10×放大倍数下达到AUC 0.89。对于TRG0,40×放大倍数下的模型达到了精确度0.67、灵敏度0.67和特异度0.95。对于TRG1/2,达到了精确度0.92、灵敏度0.86和特异度0.89。对于TRG3,模型获得了精确度0.71、灵敏度0.83和特异度0.88。为了寻找治疗反应与病理图像之间的关系,我们使用类激活映射(CAM)构建了图块的视觉热图。
值得注意的是,我们发现肿瘤细胞核和TIL(肿瘤浸润淋巴细胞)似乎是该算法的潜在特征。综上所述,该多分类器是首个用于预测直肠癌不同NAT反应的多分类器。
Neoadjuvant therapy (NAT) is a major treatment option for locally advanced rectal cancer. With recent advancement of machine/deep learning algorithms, predicting the treatment response of NAT has become possible using radiological and/or pathological images.
However, programs reported thus far are limited to binary classifications, and they can only distinguish the pathological complete response (pCR). In the clinical setting, the pathological NAT responses are classified as four classes: (TRG0-3), with 0 as pCR, 1 as moderate response, 2 as minimal response and 3 as poor response.
Therefore, the actual clinical need for risk stratification remains unmet. By using ResNet (Residual Neural Network), we developed a multi-class classifier based on Hematoxylin-Eosin (HE) images to divide the response to three groups (TRG0, TRG1/2, and TRG3).
Overall, the model achieved the AUC 0. 97 at 40× magnification and AUC 0. 89 at 10× magnification. For TRG0, the model under 40× magnification achieved a precision of 0. 67, a sensitivity of 0. 67, and a specificity of 0. 95. For TRG1/2, a precision of 0. 92, a sensitivity of 0. 86, and a specificity of 0.
89 were achieved. For TRG3, the model obtained a precision of 0. 71, a sensitivity of 0. 83, and a specificity of 0. 88. To find the relationship between the treatment response and pathological images, we constructed a visual heat map of tiles using Class Activation Mapping (CAM).
Notably, we found that tumor nuclei and tumor-infiltrating lymphocytes appeared to be potential features of the algorithm. Taken together, this multi-class classifier represents the first of its kind to predict different NAT responses in rectal cancer.
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