Identification of potential agents for thymoma by integrated analyses of differentially expressed tumour‑associated genes and molecular docking experiments

Abstract

Thymoma, derived from the epithelial cells of the thymus, is a rare malignant tumour type. Following diagnosis with thymoma, patients generally undergo surgical treatment. However, patients with advanced-stage disease are only candidates for chemotherapy and have poor survival. Therefore, it is urgently required to explore effective chemotherapeutic agents for the treatment of thymoma. In the present study, a Bioinformatics analysis was performed to identify novel drugs for thymoma. Differentially expressed genes (DEGs) in thymoma were obtained by Gene Expression Profiling Interactive Analysis. Subsequently, these genes were processed by Connectivity Map analysis to identify suitable compounds. In addition, Metascape software was used to verify drug and target binding. Molecular docking technology was used to verify drug and target binding. Finally, absorption, distribution, metabolism and excretion parameters in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database were used for drug screening and for evaluation of the potential clinical value. In total, 2,447 DEGs, including 2,204 upregulated and 243 downregulated genes, were identified from 118 thymoma patients and 339 normal samples. The top 10 drugs displaying the most significant negative correlations were fulvestrant, hesperetin, zidovudine, hydrocortisone, rolitetracycline, ellipticine, sirolimus, quinisocaine, oestradiol (estradiol) and harmine. The predicted targets of these drugs were then confirmed. The score for the association between estrogen receptor 1 (ESR1) and fulvestrant was 0.99. According to the molecular docking analysis, the total scores for the interaction between ESR1 were 10.26, and those for the interaction between tamoxifen and ESR1 were 6.60. The oral bioavailability (%), drug-likeness and drug half-life for hesperetin were 70.31, 0.27 and 15.78, respectively; those for oestradiol were 53.56, 0.32 and 3.50, respectively; and those for harmine were 56.80, 0.13 and 5.04, respectively. In conclusion, several potential therapeutic drugs for thymoma were identified in the present study. The results suggested that the compounds, including fulvestrant, estradiol, hesperetin and ellipticine, represent the most likely drugs for the treatment of thymoma. Future studies should focus on testing these novel compounds in vitro and in vivo.