Gene and microRNA expression predictive of tumour response in patients treated with pCRT for LARC

The goal of this work is to find robust predictors of tumor response to preoperative chemoradiotherapy in LARC patients. Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, tumour response to pCRT is not uniform and there are no effective predictive methods. This study investigated whether specific gene and miRNA expression is associated with response to pCRT. Tissue biopsies were obtained from patients before pCRT and resection. Gene and miRNA expression was analyzed using one-color microarrays technique comparing signatures between responders (R) and not responders(NR), as measured by tumour regression grade (TRG). Two groups composed by 38 “exploration cohort” and 21 “validation cohort” LARC patients respectively were considered, for a total of 32 NR and 27 R patients. In the first cohort, SAM Two Class identified 256 genes and 29 miRNAs differentially expressed between NR and R. The anti-correlation analysis showed that the same 8 miRNA interacted with different networks of transcripts. The miR-630 appeared only with NR patients and was anti-correlated with a single transcript: RAB5B. After PAM, resulted as strong predictors of tumour responsen the following 8 transcripts: TMEM188, ITGA2, NRG, TRAM1, BCL2L13, MYO1B, KLF7 and GTSE1. Using this gene set, an unsupervised cluster analysis applied to the second cohort assigned the patients to the NR or R group with 85.7% accuracy with a sensitivity of 90% and a specificity of 82%. All the three parametres reached 100% when the two cohorts were considered together. Tissue biopsies were obtained from patients before pCRT and resection. Two groups composed by 38 and 21 LARC patients respectively were considered, for a total of 32 NR and 27 R patients both for gene and miRNA expression experiments