论文标题

基于成像的组织学特征可预测非小细胞肺癌的MET改变

Imaging-based histological features are predictive of MET alterations in Non-Small Cell Lung Cancer

论文作者

Joshi, Rohan P., Osinski, Bolesław L., Beig, Niha, Sha, Lingdao, Ingale, Kshitij, Stumpe, Martin C.

论文摘要

MET是一种原始癌基因,其在非小细胞肺癌中的体细胞激活导致细胞生长和肿瘤进展增加。 MET改变的两个主要类别是基因扩增和外显子14缺失,这两个都是治疗靶标,并且可以使用现有的分子测定。但是,现有的测试受到其对有价值的组织的消费,成本和复杂性的限制,这些组织可防止使用广泛使用。 MET改变可能会对细胞形态产生影响,量化这些关联可能为基于形态学的筛查工具的研究和开发开辟新的途径。使用H&E染色的全幻灯片图像(WSIS),我们研究了不同细胞形态学特征与MET扩增的关联,并满足了外显子14缺失。我们发现,肿瘤浸润淋巴细胞和肿瘤细胞的细胞形状,颜色,灰度强度和基于纹理的特征与MET扩增或MET EXON 14缺失病例相遇。单个细胞特征与MET改变的关联表明,预测模型可以将MET野生型与MET扩增或MET Exon 14缺失区分开。因此,我们开发了一个L1占层化的逻辑回归模型,在交叉验证中达到了0.77 +/- 0.05SD的接收器操作特征曲线(ROC-AUC)下的平均面积,并在独立的保留测试集中达到0.77。一组稀疏的43组具有区分这些类别,其中包括类似于单变量分析以及组织中肿瘤细胞百分比的特征。我们的研究表明,MET改变会导致肿瘤细胞和淋巴细胞中可检测到的形态信号。这些结果表明,基于H&E染色的WSI的低成本预测模型的发展可能会改善MET改变肿瘤的筛查。

MET is a proto-oncogene whose somatic activation in non-small cell lung cancer leads to increased cell growth and tumor progression. The two major classes of MET alterations are gene amplification and exon 14 deletion, both of which are therapeutic targets and detectable using existing molecular assays. However, existing tests are limited by their consumption of valuable tissue, cost and complexity that prevent widespread use. MET alterations could have an effect on cell morphology, and quantifying these associations could open new avenues for research and development of morphology-based screening tools. Using H&E-stained whole slide images (WSIs), we investigated the association of distinct cell-morphological features with MET amplifications and MET exon 14 deletions. We found that cell shape, color, grayscale intensity and texture-based features from both tumor infiltrating lymphocytes and tumor cells distinguished MET wild-type from MET amplified or MET exon 14 deletion cases. The association of individual cell features with MET alterations suggested a predictive model could distinguish MET wild-type from MET amplification or MET exon 14 deletion. We therefore developed an L1-penalized logistic regression model, achieving a mean Area Under the Receiver Operating Characteristic Curve (ROC-AUC) of 0.77 +/- 0.05sd in cross-validation and 0.77 on an independent holdout test set. A sparse set of 43 features differentiated these classes, which included features similar to what was found in the univariate analysis as well as the percent of tumor cells in the tissue. Our study demonstrates that MET alterations result in a detectable morphological signal in tumor cells and lymphocytes. These results suggest that development of low-cost predictive models based on H&E-stained WSIs may improve screening for MET altered tumors.

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