Identification of lung cancer gene markers through kernel maximum mean discrepancy and information entropy

Abstract

Background: The early diagnosis of lung cancer has been a critical problem in clinical practice for a long time and identifying differentially expressed gene as disease marker is a promising solution. However, the most existing gene differential expression analysis (DEA) methods have two main drawbacks: First, these methods are based on fixed statistical hypotheses and not always effective; Second, these methods can not identify a certain expression level boundary when there is no obvious expression level gap between control and experiment groups. Methods: This paper proposed a novel approach to identify marker genes and gene expression level boundary for lung cancer. By calculating a kernel maximum mean discrepancy, our method can evaluate the expression differences between normal, normal adjacent to tumor (NAT) and tumor samples. For the potential marker genes, the expression level boundaries among different groups are defined with the information entropy method. Results: Compared with two conventional methods t-test and fold change, the top average ranked genes selected by our method can achieve better performance under all metrics in the 10-fold cross-validation. Then GO and KEGG enrichment analysis are conducted to explore the biological function of the top 100 ranked genes. At last, we choose the top 10 average ranked genes as lung cancer markers and their expression boundaries are calculated and reported. Conclusion: The proposed approach is effective to identify gene markers for lung cancer diagnosis. It is not only more accurate than conventional DEA methods but also provides a reliable method to identify the gene expression level boundaries.