Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning Algorithm

It is difficult to determine which patients with stage I and II colorectal cancer are at high risk of recurrence, qualifying them to undergo adjuvant chemotherapy. In this study, we aimed to determine a gene signature using gene expression data that could successfully identify high risk of recurrenc...

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Main Authors: Han-Ching Chan, Amrita Chattopadhyay, Eric Y. Chuang, Tzu-Pin Lu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.631056/full
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spelling doaj-cd7daa311cce48928df7957d3fc25a1b2021-02-22T14:10:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011110.3389/fonc.2021.631056631056Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning AlgorithmHan-Ching Chan0Amrita Chattopadhyay1Eric Y. Chuang2Eric Y. Chuang3Tzu-Pin Lu4Tzu-Pin Lu5Department of Public Health, College of Public Health, National Taiwan University, Institute of Epidemiology and Preventive Medicine, Taipei, TaiwanBioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, TaiwanBioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, TaiwanDepartment of Electrical Engineering, Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, TaiwanDepartment of Public Health, College of Public Health, National Taiwan University, Institute of Epidemiology and Preventive Medicine, Taipei, TaiwanBioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, TaiwanIt is difficult to determine which patients with stage I and II colorectal cancer are at high risk of recurrence, qualifying them to undergo adjuvant chemotherapy. In this study, we aimed to determine a gene signature using gene expression data that could successfully identify high risk of recurrence among stage I and II colorectal cancer patients. First, a synthetic minority oversampling technique was used to address the problem of imbalanced data due to rare recurrence events. We then applied a sequential workflow of three methods (significance analysis of microarrays, logistic regression, and recursive feature elimination) to identify genes differentially expressed between patients with and without recurrence. To stabilize the prediction algorithm, we repeated the above processes on 10 subsets by bagging the training data set and then used support vector machine methods to construct the prediction models. The final predictions were determined by majority voting. The 10 models, using 51 differentially expressed genes, successfully predicted a high risk of recurrence within 3 years in the training data set, with a sensitivity of 91.18%. For the validation data sets, the sensitivity of the prediction with samples from two other countries was 80.00% and 91.67%. These prediction models can potentially function as a tool to decide if adjuvant chemotherapy should be administered after surgery for patients with stage I and II colorectal cancer.https://www.frontiersin.org/articles/10.3389/fonc.2021.631056/fullcolorectal cancermachine learninggene expressionprognostic signatureensemble
collection DOAJ
language English
format Article
sources DOAJ
author Han-Ching Chan
Amrita Chattopadhyay
Eric Y. Chuang
Eric Y. Chuang
Tzu-Pin Lu
Tzu-Pin Lu
spellingShingle Han-Ching Chan
Amrita Chattopadhyay
Eric Y. Chuang
Eric Y. Chuang
Tzu-Pin Lu
Tzu-Pin Lu
Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning Algorithm
Frontiers in Oncology
colorectal cancer
machine learning
gene expression
prognostic signature
ensemble
author_facet Han-Ching Chan
Amrita Chattopadhyay
Eric Y. Chuang
Eric Y. Chuang
Tzu-Pin Lu
Tzu-Pin Lu
author_sort Han-Ching Chan
title Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning Algorithm
title_short Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning Algorithm
title_full Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning Algorithm
title_fullStr Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning Algorithm
title_full_unstemmed Development of a Gene-Based Prediction Model for Recurrence of Colorectal Cancer Using an Ensemble Learning Algorithm
title_sort development of a gene-based prediction model for recurrence of colorectal cancer using an ensemble learning algorithm
publisher Frontiers Media S.A.
series Frontiers in Oncology
issn 2234-943X
publishDate 2021-02-01
description It is difficult to determine which patients with stage I and II colorectal cancer are at high risk of recurrence, qualifying them to undergo adjuvant chemotherapy. In this study, we aimed to determine a gene signature using gene expression data that could successfully identify high risk of recurrence among stage I and II colorectal cancer patients. First, a synthetic minority oversampling technique was used to address the problem of imbalanced data due to rare recurrence events. We then applied a sequential workflow of three methods (significance analysis of microarrays, logistic regression, and recursive feature elimination) to identify genes differentially expressed between patients with and without recurrence. To stabilize the prediction algorithm, we repeated the above processes on 10 subsets by bagging the training data set and then used support vector machine methods to construct the prediction models. The final predictions were determined by majority voting. The 10 models, using 51 differentially expressed genes, successfully predicted a high risk of recurrence within 3 years in the training data set, with a sensitivity of 91.18%. For the validation data sets, the sensitivity of the prediction with samples from two other countries was 80.00% and 91.67%. These prediction models can potentially function as a tool to decide if adjuvant chemotherapy should be administered after surgery for patients with stage I and II colorectal cancer.
topic colorectal cancer
machine learning
gene expression
prognostic signature
ensemble
url https://www.frontiersin.org/articles/10.3389/fonc.2021.631056/full
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