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Deep Learning Analysis of CT Images Reveals High-Grade Pathological Features to Predict Survival in Lung Adenocarcinoma.

ABSTRACT: We aimed to develop a deep learning (DL) model for predicting high-grade patterns in lung adenocarcinomas (ADC) and to assess the prognostic performance of model in advanced lung cancer patients who underwent neoadjuvant or definitive concurrent chemoradiation therapy (CCRT). We included 275 patients with 290 early lung ADCs from an ongoing prospective clinical trial in the training dataset, which we split into internal-training and internal-validation datasets. We constructed a diagnostic DL model of high-grade patterns of lung ADC considering both morphologic view of the tumor and context view of the area surrounding the tumor (MC3DN; morphologic-view context-view 3D network). Validation was performed on an independent dataset of 417 patients with advanced non-small cell lung cancer who underwent neoadjuvant or definitive CCRT. The area under the curve value of the DL model was 0.8 for the prediction of high-grade histologic patterns such as micropapillary and solid patterns (MPSol). When our model was applied to the validation set, a high probability of MPSol was associated with worse overall survival (probability of MPSol >0.5 vs. <0.5; 5-year OS rate 56.1% vs. 70.7%), indicating that our model could predict the clinical outcomes of advanced lung cancer patients. The subgroup with a high probability of MPSol estimated by the DL model showed a 1.76-fold higher risk of death (HR 1.76, 95% CI 1.16-2.68). Our DL model can be useful in estimating high-grade histologic patterns in lung ADCs and predicting clinical outcomes of patients with advanced lung cancer who underwent neoadjuvant or definitive CCRT.

SUBMITTER: Choi Y

PROVIDER: S-EPMC8391458 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PURPOSE:Convolutional neural networks have become rapidly popular for image recognition and image analysis because of its powerful potential. In this paper, we developed a method for classifying subtypes of lung adenocarcinoma from pathological images using neural network whose that can evaluate phenotypic features from wider area to consider cellular distributions. METHODS:In order to recognize the types of tumors, we need not only to detail features of cells, but also to incorporate statistical distribution of the different types of cells. Variants of autoencoders as building blocks of pre-trained convolutional layers of neural networks are implemented. A sparse deep autoencoder which minimizes local information entropy on the encoding layer is then proposed and applied to images of size [Formula: see text]. We applied this model for feature extraction from pathological images of lung adenocarcinoma, which is comprised of three transcriptome subtypes previously defined by the Cancer Genome Atlas network. Since the tumor tissue is composed of heterogeneous cell populations, recognition of tumor transcriptome subtypes requires more information than local pattern of cells. The parameters extracted using this approach will then be used in multiple reduction stages to perform classification on larger images. RESULTS:We were able to demonstrate that these networks successfully recognize morphological features of lung adenocarcinoma. We also performed classification and reconstruction experiments to compare the outputs of the variants. The results showed that the larger input image that covers a certain area of the tissue is required to recognize transcriptome subtypes. The sparse autoencoder network with [Formula: see text] input provides a 98.9% classification accuracy. CONCLUSION:This study shows the potential of autoencoders as a feature extraction paradigm and paves the way for a whole slide image analysis tool to predict molecular subtypes of tumors from pathological features.

Project description:Convolutional neural networks (CNNs) are revolutionizing digital pathology by enabling machine learning-based classification of a variety of phenotypes from hematoxylin and eosin (H&E) whole slide images (WSIs), but the interpretation of CNNs remains difficult. Most studies have considered interpretability in a post hoc fashion, e.g. by presenting example regions with strongly predicted class labels. However, such an approach does not explain the biological features that contribute to correct predictions. To address this problem, here we investigate the interpretability of H&E-derived CNN features (the feature weights in the final layer of a transfer-learning-based architecture). While many studies have incorporated CNN features into predictive models, there has been little empirical study of their properties. We show such features can be construed as abstract morphological genes ("mones") with strong independent associations to biological phenotypes. Many mones are specific to individual cancer types, while others are found in multiple cancers especially from related tissue types. We also observe that mone-mone correlations are strong and robustly preserved across related cancers. Importantly, linear mone-based classifiers can very accurately separate 38 distinct classes (19 tumor types and their adjacent normals, AUC = [Formula: see text] for each class prediction), and linear classifiers are also highly effective for universal tumor detection (AUC = [Formula: see text]). This linearity provides evidence that individual mones or correlated mone clusters may be associated with interpretable histopathological features or other patient characteristics. In particular, the statistical similarity of mones to gene expression values allows integrative mone analysis via expression-based bioinformatics approaches. We observe strong correlations between individual mones and individual gene expression values, notably mones associated with collagen gene expression in ovarian cancer. Mone-expression comparisons also indicate that immunoglobulin expression can be identified using mones in colon adenocarcinoma and that immune activity can be identified across multiple cancer types, and we verify these findings by expert histopathological review. Our work demonstrates that mones provide a morphological H&E decomposition that can be effectively associated with diverse phenotypes, analogous to the interpretability of transcription via gene expression values. Our work also demonstrates mones can be interpreted without using a classifier as a proxy.

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Deep Learning Analysis of CT Images Reveals High-Grade Pathological Features to Predict Survival in Lung Adenocarcinoma.

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