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Evaluating the Microsatellite Instability of Colorectal Cancer Based on Multimodal Deep Learning Integrating Histopathological and Molecular Data
Microsatellite instability (MSI), an important biomarker for immunotherapy and the diagnosis of Lynch syndrome, refers to the change of microsatellite (MS) sequence length caused by insertion or deletion during DNA replication. However, traditional wet-lab experiment-based MSI detection is time-cons...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295995/ https://www.ncbi.nlm.nih.gov/pubmed/35865460 http://dx.doi.org/10.3389/fonc.2022.925079 |
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author | Qiu, Wenjing Yang, Jiasheng Wang, Bing Yang, Min Tian, Geng Wang, Peizhen Yang, Jialiang |
author_facet | Qiu, Wenjing Yang, Jiasheng Wang, Bing Yang, Min Tian, Geng Wang, Peizhen Yang, Jialiang |
author_sort | Qiu, Wenjing |
collection | PubMed |
description | Microsatellite instability (MSI), an important biomarker for immunotherapy and the diagnosis of Lynch syndrome, refers to the change of microsatellite (MS) sequence length caused by insertion or deletion during DNA replication. However, traditional wet-lab experiment-based MSI detection is time-consuming and relies on experimental conditions. In addition, a comprehensive study on the associations between MSI status and various molecules like mRNA and miRNA has not been performed. In this study, we first studied the association between MSI status and several molecules including mRNA, miRNA, lncRNA, DNA methylation, and copy number variation (CNV) using colorectal cancer data from The Cancer Genome Atlas (TCGA). Then, we developed a novel deep learning framework to predict MSI status based solely on hematoxylin and eosin (H&E) staining images, and combined the H&E image with the above-mentioned molecules by multimodal compact bilinear pooling. Our results showed that there were significant differences in mRNA, miRNA, and lncRNA between the high microsatellite instability (MSI-H) patient group and the low microsatellite instability or microsatellite stability (MSI-L/MSS) patient group. By using the H&E image alone, one can predict MSI status with an acceptable prediction area under the curve (AUC) of 0.809 in 5-fold cross-validation. The fusion models integrating H&E image with a single type of molecule have higher prediction accuracies than that using H&E image alone, with the highest AUC of 0.952 achieved when combining H&E image with DNA methylation data. However, prediction accuracy will decrease when combining H&E image with all types of molecular data. In conclusion, combining H&E image with deep learning can predict the MSI status of colorectal cancer, the accuracy of which can further be improved by integrating appropriate molecular data. This study may have clinical significance in practice. |
format | Online Article Text |
id | pubmed-9295995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92959952022-07-20 Evaluating the Microsatellite Instability of Colorectal Cancer Based on Multimodal Deep Learning Integrating Histopathological and Molecular Data Qiu, Wenjing Yang, Jiasheng Wang, Bing Yang, Min Tian, Geng Wang, Peizhen Yang, Jialiang Front Oncol Oncology Microsatellite instability (MSI), an important biomarker for immunotherapy and the diagnosis of Lynch syndrome, refers to the change of microsatellite (MS) sequence length caused by insertion or deletion during DNA replication. However, traditional wet-lab experiment-based MSI detection is time-consuming and relies on experimental conditions. In addition, a comprehensive study on the associations between MSI status and various molecules like mRNA and miRNA has not been performed. In this study, we first studied the association between MSI status and several molecules including mRNA, miRNA, lncRNA, DNA methylation, and copy number variation (CNV) using colorectal cancer data from The Cancer Genome Atlas (TCGA). Then, we developed a novel deep learning framework to predict MSI status based solely on hematoxylin and eosin (H&E) staining images, and combined the H&E image with the above-mentioned molecules by multimodal compact bilinear pooling. Our results showed that there were significant differences in mRNA, miRNA, and lncRNA between the high microsatellite instability (MSI-H) patient group and the low microsatellite instability or microsatellite stability (MSI-L/MSS) patient group. By using the H&E image alone, one can predict MSI status with an acceptable prediction area under the curve (AUC) of 0.809 in 5-fold cross-validation. The fusion models integrating H&E image with a single type of molecule have higher prediction accuracies than that using H&E image alone, with the highest AUC of 0.952 achieved when combining H&E image with DNA methylation data. However, prediction accuracy will decrease when combining H&E image with all types of molecular data. In conclusion, combining H&E image with deep learning can predict the MSI status of colorectal cancer, the accuracy of which can further be improved by integrating appropriate molecular data. This study may have clinical significance in practice. Frontiers Media S.A. 2022-07-05 /pmc/articles/PMC9295995/ /pubmed/35865460 http://dx.doi.org/10.3389/fonc.2022.925079 Text en Copyright © 2022 Qiu, Yang, Wang, Yang, Tian, Wang and Yang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Qiu, Wenjing Yang, Jiasheng Wang, Bing Yang, Min Tian, Geng Wang, Peizhen Yang, Jialiang Evaluating the Microsatellite Instability of Colorectal Cancer Based on Multimodal Deep Learning Integrating Histopathological and Molecular Data |
title | Evaluating the Microsatellite Instability of Colorectal Cancer Based on Multimodal Deep Learning Integrating Histopathological and Molecular Data |
title_full | Evaluating the Microsatellite Instability of Colorectal Cancer Based on Multimodal Deep Learning Integrating Histopathological and Molecular Data |
title_fullStr | Evaluating the Microsatellite Instability of Colorectal Cancer Based on Multimodal Deep Learning Integrating Histopathological and Molecular Data |
title_full_unstemmed | Evaluating the Microsatellite Instability of Colorectal Cancer Based on Multimodal Deep Learning Integrating Histopathological and Molecular Data |
title_short | Evaluating the Microsatellite Instability of Colorectal Cancer Based on Multimodal Deep Learning Integrating Histopathological and Molecular Data |
title_sort | evaluating the microsatellite instability of colorectal cancer based on multimodal deep learning integrating histopathological and molecular data |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295995/ https://www.ncbi.nlm.nih.gov/pubmed/35865460 http://dx.doi.org/10.3389/fonc.2022.925079 |
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