An Unsupervised Deep Learning-Based Model Using Multiomics Data to Predict Prognosis of Patients with Stomach Adenocarcinoma
Sizhen Chen, Yiteng Zang, Biyun Xu, Beier Lu, Rongji Ma, Pengcheng Miao, Bingwei Chen
Abstract
Object. This study is aimed at constructing a deep learning architecture of the autoencoder to integrate multiomics data and identify the risk of patients with stomach adenocarcinoma. Methods. Patients (363 in total) with stomach adenocarcinoma from The Cancer Genome Atlas (TCGA) cohort were included. An autoencoder was constructed to integrate the RNA sequencing, miRNA sequencing, and methylation data. The features of the bottleneck layer were used to perform the <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>k</a:mi> </a:math> -means clustering algorithm to obtain different subgroups for evaluating the prognosis-related risk of stomach adenocarcinoma. The model’s robustness was verified using a 10-fold cross-validation (CV). Survival was analyzed by the Kaplan-Meier method. Univariate and multivariate Cox regression was used to estimate hazard risk. The model was validated in three independent cohorts with different endpoints. Results. The patients were divided into low-risk and high-risk groups according to the <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>k</c:mi> </c:math> -means clustering algorithm. The high-risk group had a significantly higher risk of poor survival (log-rank <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> </e:math> value = <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mn>2.80</g:mn> <g:mi>e</g:mi> <g:mo>−</g:mo> <g:mn>06</g:mn> </g:math> ; <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mtext>adjusted</i:mtext> <i:mtext> </i:mtext> <i:mtext>hazard</i:mtext> <i:mtext> </i:mtext> <i:mtext>ratio</i:mtext> <i:mo>=</i:mo> <i:mn>2.386</i:mn> </i:math> , 95% confidence interval: 1.607~3.543), a concordance index (C-index) of 0.714, and a Brier score of 0.184. The model performed well both in the 10-fold CV procedure and three independent cohorts from the Gene Expression Omnibus (GEO) repository. Conclusions. A robust and generalizable model based on the autoencoder was proposed to integrate multiomics data and predict the prognosis of patients with stomach adenocarcinoma. The model demonstrates better performance than two alternative approaches on prognosis prediction. The results might provide the grounds for further exploring the potential biomarkers to predict the prognosis of patients with stomach adenocarcinoma.