论文标题

使用MMR标记的大肠癌中基于深度学习的预测

Deep Learning based Prediction of MSI using MMR Markers in Colorectal Cancer

论文作者

Awan, Ruqayya, Nimir, Mohammed, Raza, Shan E Ahmed, Bilal, Mohsin, Lotz, Johannes, Snead, David, Robinson, Andrew, Rajpoot, Nasir

论文摘要

结直肠癌的准确诊断和分子分析对于计划患者的最佳治疗选择至关重要。微卫星不稳定性(MSI)或不匹配修复(MMR)状态在适当的治疗选择中起着至关重要的作用,具有预后的意义,用于研究患有潜在遗传疾病(Lynch综合征)的患者的可能性。 NICE建议应为所有CRC患者提供MMR/MSI测试。免疫组织化学通常用于评估MMR状态,随后根据需要进行的分子测试。这会产生巨大的额外费用,需要额外的资源。引入可以从目标图像预测MSI或MMR状态的自动化方法可以大大降低与MMR测试相关的成本。与以前关于MSI预测的研究涉及使用粗标签(MSI与微卫星稳定(MSS))训练CNN的研究不同,我们已利用细粒MMR标签来训练。在本文中,我们介绍了使用CK8/18或H&E染色的单个目标幻灯片在两个阶段过程中预测MSI状态的工作。首先,我们训练了一个多头卷积神经网络模型,每个头部负责预测一种MMR蛋白表达式。为此,我们将MMR染色幻灯片的注册作为预处理步骤。在第二阶段,使用MMR预测图计算出的统计特征用于最终的MSI预测。我们的结果表明,与以前仅使用粗标签的方法相比,可以通过合并细粒的MMR标签来改进MSI分类。

The accurate diagnosis and molecular profiling of colorectal cancers are critical for planning the best treatment options for patients. Microsatellite instability (MSI) or mismatch repair (MMR) status plays a vital role in appropriate treatment selection, has prognostic implications and is used to investigate the possibility of patients having underlying genetic disorders (Lynch syndrome). NICE recommends that all CRC patients should be offered MMR/MSI testing. Immunohistochemistry is commonly used to assess MMR status with subsequent molecular testing performed as required. This incurs significant extra costs and requires additional resources. The introduction of automated methods that can predict MSI or MMR status from a target image could substantially reduce the cost associated with MMR testing. Unlike previous studies on MSI prediction involving training a CNN using coarse labels (MSI vs Microsatellite Stable (MSS)), we have utilised fine-grain MMR labels for training purposes. In this paper, we present our work on predicting MSI status in a two-stage process using a single target slide either stained with CK8/18 or H&E. First, we trained a multi-headed convolutional neural network model where each head was responsible for predicting one of the MMR protein expressions. To this end, we performed the registration of MMR stained slides to the target slide as a pre-processing step. In the second stage, statistical features computed from the MMR prediction maps were used for the final MSI prediction. Our results demonstrated that MSI classification can be improved by incorporating fine-grained MMR labels in comparison to the previous approaches in which only coarse labels were utilised.

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