352. Gene and MicroRNA Expression Predictive of Tumour Response in Patients Treated with Preoperative Chemoradiotherapy for Rectal Cancer

Background Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, the response to pCRT is not uniform, and there is no effective method to predict tumour response to pCRT. Identification of patients not responsive to pCRT could avoid useless exposure to radiation or chemotherapy which is associated with adverse effects. Moreover, the identification of pathological complete response could select patients candidated to a more preserving surgery. The aim of this study is to investigate whether gene and micro-RNA (miRNA) expression profiling is associated with rectal cancer response to pCRT. Materials and methods Tissue biopsies were obtained from patients with mid-low LARC, before pCRT. All the patients underwent standard pCRT followed by resection. All surgical specimens underwent standardized histopathological examination. The biopsies with ≥50% of cancer tissue were considered for the experiment. Gene and miRNA expression was analyzed using one color microarrays technique (Agilent®), after RNA isolation. The data were normalized intra- and inter-array, filtered and then clustered. Gene and miRNA expression was compared between responders (R) and non responders (NR) as measured by histopathological tumour regression grade (TRG). Validation of microarrays data was made by quantitative PCR (qPCR). Results Thirty-eight patients, 16 (42%) R (TRG1-2) and 22 (58%) NR (TRG3-5), were considered. Using SAM (Significance Analysis of Microarrays) two class, 256 genes were found differentially expressed between NR and R (188 over- and 68 down-expressed). Performing PAM (Prediction Analysis for Microarray), 12 genes were strongly predictive of tumour response. Using SAM two class, 30 miRNAs were found differentially expressed between NR and R (24 over- and 6 down-expressed). Anti-correlation analyses, using MAGIA (miRNA and genes integrated analysis), revealed the same 8 miRNAs both in NR and R group, except for miR-630, over-expressed only in NR group. ABCC2 gene, miR-7, miR-182, miR-200a, miR-630, miR-638, and miR-1300 were validated by qPCR, confirming the data obtained by microarray analysis. Conclusions Pre-treatment gene and miRNA expression profiling may be helpful to predict response to pCRT in LARC. Further analyses to confirm these findings are required.