Identification of potential genes and pathways for response prediction of neoadjuvant chemoradiotherapy in patients with rectal cancer by systemic biological analysis

摘要

Currently, neoadjuvant chemoradiotherapy (CRT) followed by radical surgery is the standard of care for locally advanced rectal cancer. However, to the best of our knowledge, there are no effective biomarkers for predicting patients who may benefit from neoadjuvant treatment. The aim of the current study was to screen potential crucial genes and pathways associated with the response to CRT in rectal cancer, and provide valid biological information to assist further investigation of CRT optimization. In the current study, differentially expressed (DE) genes were identified from the tumor samples of responders and non-responders to neoadjuvant CRT in the gene expression profile. Seven hub genes and one significant module were identified from the protein-protein interaction (PPI) network. Functional enrichment analysis of all the DE genes and the hub genes, retrieved from PPI network analysis, revealed their associations with CRT response. Genes were identified that may be used to discriminate patients who would or would not clinically benefit from neoadjuvant CRT. Several important pathways enriched by the DE genes, hub genes and selected module were identified, and revealed to be closely associated with radiation response, including excision repair, homologous recombination, Ras signaling pathway, the forkhead box O signaling pathway, focal adhesion and the Wnt signaling pathway. In conclusion, the current study demonstrated that the identified gene signatures and pathways may be used as molecular biomarkers for predicting CRT response. Furthermore, combinations of these biomarkers may be helpful for optimizing CRT treatment and promoting understanding of the molecular basis of response differences; this needs to be confirmed by further experiments.