Dataset Information

Weighted-Support Vector Machine Learning Classifier of Circulating Cytokine Biomarkers to Predict Radiation-Induced Lung Fibrosis in Non-Small-Cell Lung Cancer Patients.

ABSTRACT:

Background

Radiation-induced lung fibrosis (RILF) is an important late toxicity in patients with non-small-cell lung cancer (NSCLC) after radiotherapy (RT). Clinically significant RILF can impact quality of life and/or cause non-cancer related death. This study aimed to determine whether pre-treatment plasma cytokine levels have a significant effect on the risk of RILF and investigate the abilities of machine learning algorithms for risk prediction.

Methods

This is a secondary analysis of prospective studies from two academic cancer centers. The primary endpoint was grade≥2 (RILF2), classified according to a system consistent with the consensus recommendation of an expert panel of the AAPM task for normal tissue toxicity. Eligible patients must have at least 6 months' follow-up after radiotherapy commencement. Baseline levels of 30 cytokines, dosimetric, and clinical characteristics were analyzed. Support vector machine (SVM) algorithm was applied for model development. Data from one center was used for model training and development; and data of another center was applied as an independent external validation.

Results

There were 57 and 37 eligible patients in training and validation datasets, with 14 and 16.2% RILF2, respectively. Of the 30 plasma cytokines evaluated, SVM identified baseline circulating CCL4 as the most significant cytokine associated with RILF2 risk in both datasets (P = 0.003 and 0.07, for training and test sets, respectively). An SVM classifier predictive of RILF2 was generated in Cohort 1 with CCL4, mean lung dose (MLD) and chemotherapy as key model features. This classifier was validated in Cohort 2 with accuracy of 0.757 and area under the curve (AUC) of 0.855.

Conclusions

Using machine learning, this study constructed and validated a weighted-SVM classifier incorporating circulating CCL4 levels with significant dosimetric and clinical parameters which predicts RILF2 risk with a reasonable accuracy. Further study with larger sample size is needed to validate the role of CCL4, and this SVM classifier in RILF2.

SUBMITTER: Yu H

PROVIDER: S-EPMC7883680 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:The present study aimed to identify the feature genes associated with smoking in lung adenocarcinoma (LAC) samples and explore the underlying mechanism. Three gene expression datasets of LAC samples were downloaded from the Gene Expression Omnibus database through pre?set criteria and the expression data were processed using meta?analysis. Differentially expressed genes (DEGs) between LAC samples of smokers and non?smokers were identified using limma package in R. The classification accuracy of selected DEGs were visualized using hierarchical clustering analysis in R language. A protein?protein interaction (PPI) network was constructed using gene interaction data from the Human Protein Reference Database for the DEGs. Betweenness centrality was calculated for each node in the network and genes with the greatest BC values were utilized for the construction of the support vector machine (SVM) classifier. The dataset GSE43458 was used as the training dataset for the construction and the other datasets (GSE12667 and GSE10072) were used as the validation datasets. The classification accuracy of the classifier was tested using sensitivity, specificity, positive predictive value, negative predictive value and area under curve parameters with the pROC package in R language. The feature genes in the SVM classifier were subjected to pathway enrichment analysis using Fisher's exact test. A total of 347 genes were identified to be differentially expressed between samples of smokers and non?smokers. The PPI network of DEGs were comprised of 202 nodes and 300 edges. An SVM classifier comprised of 26 feature genes was constructed to distinguish between different LAC samples, with prediction accuracies for the GSE43458, GSE12667 and GSE10072 datasets of 100, 100 and 94.83%, respectively. Furthermore, the 26 feature genes that were significantly enriched in 9 overrepresented biological pathways, including extracellular matrix?receptor interaction, proteoglycans in cancer, cell adhesion molecules, p53 signaling pathway, microRNAs in cancer and apoptosis, were identified to be smoking?related genes in LAC. In conclusion, an SVM classifier with a high prediction accuracy for smoking and non?smoking samples was obtained. The genes in the classifier may likely be the potential feature genes associated with the development of patients with LAC who smoke.

Project description:In this study, gene expression profiles of osteosarcoma (OS) were analyzed to identify critical genes associated with metastasis. Five gene expression datasets were screened and downloaded from Gene Expression Omnibus (GEO). Following assessment by MetaQC, the dataset GSE9508 was excluded for poor quality. Subsequently, differentially expressed genes (DEGs) between metastatic and non-metastatic OS were identified using meta?analysis. A protein-protein interaction (PPI) network was constructed with information from Human Protein Reference Database (HPRD) for the DEGs. Betweenness centrality (BC) was calculated for each node in the network and top featured genes ranked by BC were selected out to construct support vector machine (SVM) classifier using the training set GSE21257, which was then validated using the other three independent datasets. Pathway enrichment analysis was performed for the featured genes using Fisher's exact test. A total of 353 DEGs were identified and a PPI network including 164 nodes and 272 edges was then constructed. The top 64 featured genes ranked by BC were included in the SVM classifier. The SVM classifier exhibited high prediction accuracies in all of the 4 datasets, with accuracies of 100, 100, 92.6 and 100%, respectively. Further analysis of the featured genes revealed that 11 Gene Ontology (GO) biological pathways and 5 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly over-represented, including the regulation of cell proliferation, regulation of apoptosis, pathways in cancer, regulation of actin cytoskeleton and the TGF-? signaling pathway. On the whole, an SVM classifier with high prediction accuracy was constructed and validated, in which key genes associated with metastasis in OS were also revealed. These findings may promote the development of genetic diagnostic methods and may enhance our understanding of the molecular mechanisms underlying the metastasis of OS.