Study Of Screening And Prediction Of Sensitivity Biomolecular Marker In Patients With Middle And Low Locally Advanced Rectal Cancer For Preoperative Chemoradiotherapy

Background:Despite recent progress in the treatment of middle and low locally advanced rectal cancer, patients remain at risk of both local recurrence and distant metastasis. Preoperative chemoradiotherapy or radiation therapy for middle and low locally advanced rectal cancer is a widely practiced treatment before surgical excision.Preoperative chemoradiotherapy have improved local control and increased disease-free and overall survival. However, there is a big difference for the sensitivity of patients with chemoradiotherapy. Therefore, the aim of this study is to screen and predict sensitivity differences biomolecular in patients with middle and low locally advanced rectal cancer for preoperative chemoradiotherapy.Methods:36patients with middle and low locally advanced rectal cancer in March2008-December2010were selected from cancer center in the First Affiliated Hospital of Kunming Medical College.36patients with middle and low locally advanced rectal cancer were confirmed by MRI.TNM stage and TRG classification were evaluated by pathology.5patients with sensitivity of the chemoradiotherapy and5patients with nonsensitivity of the chemoradiotherapy were detected by two-dimensional electrophoresis, mass spectrometry and miRNA microarray for screening and predicting sensitivity differences biomolecular marker.Results:1.23cases of middle and low locally advanced rectal cancer after anterior resection and13cases of abdominoperineal resection were opertated in36patients after chemoradiotherapy. Pathologic complete response (PCR)4cases, I stage1leases,â…¡A stage7cases,â…¢A stage3cases,â…¢B/C stage6cases and IVA stage 5cases were evaluted.2.Two-dimensional electrophoresis map comparison, analysis and identification showed six protein (PLA2, Bax, GrB2, HSPA1B, IRGQ and TNFSF6) were found high expression in tumor tissue of patients with sensitivity and3protein (NuRD, MTA1and CAGEl)were found high expression in tumor tissue of patients with nonsensitivity.3.miRNA microarray results showed in tumor tissue of patients with sensitivity,expression upregulated miRNAs hadâ‘ hsa-miR-32,â‘¡hsa-miR-27a,â‘¢hsa-miR-19a andâ‘£Has-miR-128, and expression downregulated miRNAs hadâ‘ hsa-miR-1184andâ‘¡hsa-miR-936,respectively.Conclusions:1. Preoperative chemoradiotherapy may decrease the stage of tumor and volume of tumor in the patients with middle and low locally advanced rectal cancer for chemoradiotherapy, improve local control, and increase disease-free overall and survival.2. PLA2, Bax and GrB2may be used as a candidate biomolecular marker to evalute and predict sensitivity of the patient with middle and low locally advanced rectal cancer for preoperative chemoradiotherapy.3. NuRD and MTA1can be used as a candidate biomolecular marker to evalute and predict nonsensitivity of the patient with middle and low locally advanced rectal cancer for preoperative chemoradiotherapy.4.HSPA1B, IRGQ, TNFSF6, GAGE1may be a potential biomolecular marker predicting sensitivity of the patient with middle and low locally advanced rectal cancer for preoperative chemoradiotherapy.5. hsa-miR-32, hsa-miR-27a, hsa-miR-19a and Has-miR-128may be a potential biomolecular marker for predicting sensitivity of the patient with middle and low locally advanced rectal cancer for preoperative chemoradiotherapy.