Gene and MicroRNA Expression Are Predictive of Tumor Response in Rectal Adenocarcinoma Patients Treated With Preoperative Chemoradiotherapy

Abstract

Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, tumor response to pCRT is not uniform, and there are no effective predictive methods. This study investigated whether specific gene and miRNA expression are associated with tumor response to pCRT. Tissue biopsies were obtained from patients before pCRT and resection. Gene and miRNA expression were analyzed using a one-color microarray technique that compares signatures between responders (R) and non-responders (NR), as measured based on tumor regression grade. Two groups composed of 38 "exploration cohort" and 21 "validation cohort" LARC patients were considered for a total of 32 NR and 27 R patients. In the first cohort, using SAM Two Class analysis, 256 genes and 29 miRNAs that were differentially expressed between the NR and R patients were identified. The anti-correlation analysis showed that the same 8 miRNA interacted with different networks of transcripts. The miR-630 appeared only with the NR patients and was anti-correlated with a single transcript: RAB5B. After PAM, the following eight transcripts were strong predictors of tumor response: TMEM188, ITGA2, NRG, TRAM1, BCL2L13, MYO1B, KLF7, and GTSE1. Using this gene set, an unsupervised cluster analysis was applied to the validation cohort and correctly assigned the patients to the NR or R group with 85.7% accuracy, 90% sensitivity, and 82% specificity. All three parameters reached 100% when both cohorts were considered together. In conclusion, gene and miRNA expression profiles may be helpful for predicting response to pCRT in LARC patients. J. Cell. Physiol. 232: 426-435, 2017. © 2016 Wiley Periodicals, Inc.

miR-194 as predictive biomarker of responsiveness to neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma

“…In the present study, we demonstrated that miR-194 was upregulated in responders patients by analysing its expression profile in a cohort of patients with LARC, in which we performed a miRNA microarray expression profile analysis 14. Recent data have shown that miR-194 plays an important part in tumourigenesis.…”

“…The cohort comprises n=38 patients with primary adenocarcinoma of the rectum, who underwent pCRT followed by surgery at our institution (First Surgery Clinic, University of Padova), in which we reanalysed our public microarray miRNA expression profile dataset (GEO dataset: GSE68204) 14. The microarray data platform was Agilent-021827 Human miRNA Microarray (V3).…”

Abnormal expression of mRNA, microRNA alteration and aberrant DNA methylation patterns in rectal adenocarcinoma

“…XRCC3 is over-expressed in rectal cancer patients responding to preoperative chemoradiotherapy (pCRT) followed by surgery compared with those non-responders, the deregulation of which is extensively involved in the chemo-resistance mechanism [11]. Recent articles demonstrate that two gene sets of dysregulated genes could predict pCRT response in patients with rectal adenocarcinoma, one gene set is AKR1C3, CXCL11, CXCL10, IDO1, CXCL9, MMP12, HLA-DRA and another gene set is TMEM188, ITGA2, NRG, TRAM1, BCL2L13, MYO1B, KLF7,and GTSE1 [12, 13]. microRNAs (miRNAs) are small non-coding RNAs, which negatively regulates mRNA expression of targeted genes.…”

Identification of biomarker microRNAs for predicting the response of colorectal cancer to neoadjuvant chemoradiotherapy based on microRNA regulatory network

“…It is encouraging that several putative miRNA biomarkers are reportedly associated with cancer response to preoperative chemoradiotherapy [10]. At present, it is still hard to explain the difference in radiosensitivity difference among patients.…”