Application of ARHGAP8 in Predicting the Efficacy of Neoadjuvant Chemotherapy for Locally Advanced Mid-Low Rectal Cancer

Abstract

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer. Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were selected.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARHGAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the patients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expression.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups. Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue (P<0.001).The expression level of ARHGAP8 was correlated with tumor stage (P=0.024),lymph node metastasis (P=0.007),and age (P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P<0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P=0.011).The expression of ARHGAP8 was correlated with tumor size (P=0.010) and pathological stage (P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 patients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91% (29/44) patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy (P<0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86%,which was higher than that (53.33%) in the patients with high protein level of ARHGAP8 (P=0.033). Conclusion ARHGAP8 is highly expressed in the rectal cancer tissue.The patients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and development of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.