OncoTargets and Therapy (May 2016)
miR-17-92a-1 cluster host gene (MIR17HG) evaluation and response to neoadjuvant chemoradiotherapy in rectal cancer
Abstract
Chiara Molinari,1 Samanta Salvi,1 Flavia Foca,2 Nazario Teodorani,3 Luca Saragoni,4 Maurizio Puccetti,5 Alessandro Passardi,6 Stefano Tamberi,7 Andrea Avanzolini,8 Enrico Lucci,8 Daniele Calistri1 1Biosciences Laboratory, 2Unit of Biostatistics and Clinical Trials, 3Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, 4Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, 5Pathology Unit, Santa Maria delle Croci Hospital, Ravenna, 6Department of Medical Oncology, IRST IRCCS, Meldola, 7Department of Medical Oncology, Infermi Hospital, Faenza, 8Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy Abstract: Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is the gold standard for the treatment of patients with locally advanced rectal cancer (LARC). However, response is variable, and no predictive markers have been validated. The amplification of 13q31–34 seemed to distinguish between nonresponders and responders to NCRT. The miR-17-92a-1 cluster host gene (MIR17HG), which is involved in the development, progression, and aggressiveness of colorectal cancer, and the ABCC4 gene, an ATP-binding cassette transporter, are located at this region. Moreover, the transcription factor c-Myc is closely related to MIR17HG. The aim of this study was to examine the role of MIR17HG, ABCC4, and CMYC gene copy numbers (CNs) in determining response to NCRT. We analyzed DNA CN of pretherapy biopsies from 108 LARC patients and the expression of microRNA (miR)-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1 in 34 biopsies. MIR17HG, CMYC, and ABCC4 gene CNs were frequently altered in pretreatment tumors, amplification being the most frequent alteration. With regard to response to therapy, 41% of responders showed MIR17HG deletion, while MIR17HG amplification was observed in 41% of nonresponders. With regard to pathological T stage (ypT), a higher percentage of ypT3–4 than ypT0–2 tumors showed MIR17HG amplification. Finally, a higher, albeit nonsignificant, variability in the expression of MIR17HG cluster members was detected in nonresponders compared to responders. No association was observed between clinical pathological parameters and ABCC4 or CMYC CN. Our data did not highlight a significant association between MIR17HG, CMYC, and ABCC4 gene CNs and response to NCRT in LARC. However, MIR17HG gene amplification would seem to be related to a lack of response. Evaluation of the expression of MIR17HG cluster members is warranted in a larger case series, together with functional studies, to evaluate the potential of this gene as a new predictive marker. Keywords: rectal cancer, neoadjuvant chemoradiotherapy, gene copy number, MIR17HG, ABCC4, CMYC
