Identifying Differentially Expressed Genes And Predictive Biomarkers Of Neoadjuvant Chemoradiotherapy In Rectal Carcinoma

Objective: To investigate genes related to the response of neoadjuvant chemoradiotherapy for rectal carcinoma and identify biomarkers predicting the response of this therapy? Methods: Biopsy specimens were obtained from 44 locally advanced rectal cancers underwent neoadjuvant chemoradiotherapy followed by radical surgical resection.Histology of surgical specimens were carried out in term of the 7th of American Joint Committee on Cancer(AJCC).Gene expression profilings of rectal cancer were probed by Prime View Human Gene Expression Array.Rank Products analysis were applied to identify differentially expressed genes.The Gene Ontology and DAVID 6.8 Microarray Analysis tools were used to gene functional category clustering analysis.The human protein-protein interaction(PPI)analysis was applied to select the core proteins.The core genes for the PPI interaction as predictive biomarkers of neoadjuvant chemoradiotherapy in rectal carcinomas.Results: Only pre-chemoradiotherapy T4 stage was associated with neoadjuvant chemoradiotherapy in rectal carcinoma by Univariate analysis for clinicopathological factors(p=0.013).449 Differentially expressed genes were selected between the 12 non-responders and 20 responders(False Discovery Rate<0.05)by Rank-Product algorithm.The differentially expressed genes were enriched in 167 functional category,including nitrogen metabolism,cytokine-cytokine receptor interaction,chemokine signaling pathway etc.6 core genes were mapped in the human PPI network predicting the response of the rectal carcinoma to neoadjuvant chemoradiotherapy with 100% sensitivity and 83.3% specificity.Conclusions: The present study identified differentially expressed genes.6-gene signature was able to predicted response of rectal carcinoma to neoadjuvant chemoradiotherapy with high sensitivity and specificity.