Identification of Key Genes and Pathways Associated With Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma Based on Bioinformatics Analysis

Abstract

Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of cancer-related death in China. Although paclitaxel has been shown to be effective in treating ESCC, the prolonged use of this chemical will lead to paclitaxel resistance. In order to uncover genes and pathways driving paclitaxel resistance in the progression of ESCC, bioinformatics analyses were performed based on The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database including GSE86099 and GSE161533. Differential expression analysis was performed in TCGA data and two GEO datasets to obtain differentially expressed genes (DEGs). Based on GSE161533, weighted gene co-expression network analysis (WGCNA) was conducted to identify the key modules associated with ESCC tumor status. The DEGs common to the two GEO datasets and the genes in the key modules were intersected to obtain the paclitaxel resistance-specific or non-paclitaxel resistance-specific genes, which were subjected to subsequent least absolute shrinkage and selection operator (LASSO) feature selection, whereby paclitaxel resistance-specific or non-paclitaxel resistance-specific key genes were selected. Ten machine learning models were used to validate the biological significance of these key genes; the potential therapeutic drugs for paclitaxel resistance-specific genes were also predicted. As a result, we identified 24 paclitaxel resistance-specific genes and 18 non-paclitaxel resistance-specific genes. The ESCC machine classifiers based on the key genes achieved a relatively high AUC value in the cross-validation and in an independent test set, GSE164158. A total of 207 drugs (such as bevacizumab) were predicted to be alternative therapeutics for ESCC patients with paclitaxel resistance. These results might shed light on the in-depth research of paclitaxel resistance in the context of ESCC progression.

FNDC3B and BPGM Are Involved in Human Papillomavirus-Mediated Carcinogenesis of Cervical Cancer

“…In this study, a powerful system biology algorithm, WGCNA, was used to analyze the associations among genes, and then similar genes were classified into modules and these modules were correlated with phenotypic traits ( 22 , 37 ). At present, WGCNA has been applied to identify diagnostic biomarkers and therapeutic targets in different types of tumors ( 21 , 38 , 39 ). Through analyzing the GSE138080 dataset, 16 modules were generated.…”

Cathepsin L promotes oesophageal squamous cell carcinoma development and may be associated with tumour-associated macrophages

“…ESCC expression profiling datasets GSE53624 [ 23 ], GSE161533 [ 24 ], GSE20347 [ 25 ], GSE196756 [ 26 ], and GSE188900 [ 27 ] were downloaded from the official GEO website ( https://www.ncbi.nlm.nih.gov/geo/ ). Detailed information on these datasets is provided in Table S1 .…”