title: 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.
authors.affiliation: Microarray Service, Department of Biology, CRIBI Biotechnology Centre, University of Padua, Padua, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Millino
authors.affiliation: 1st Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Isacco
authors.initials: I
authors.lastname: Maretto
authors.affiliation: Microarray Service, Department of Biology, CRIBI Biotechnology Centre, University of Padua, Padua, Italy.
authors.forename: Beniamina
authors.initials: B
authors.lastname: Pacchioni
authors.affiliation: 1st Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Digito
authors.affiliation: Department of Radiation Oncology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: De Paoli
authors.affiliation: Department of Pathology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Canzonieri
authors.affiliation: 1st Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy.|Nanoinspired Biomedicine Lab., Institute of Pediatric Research, Fondazione Città della Speranza, Padova, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: D'Angelo
authors.affiliation: 1st Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy.|Nanoinspired Biomedicine Lab., Institute of Pediatric Research, Fondazione Città della Speranza, Padova, Italy.|Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas.
authors.forename: Marco
authors.initials: M
authors.lastname: Agostini
authors.affiliation: Department of Translational Research, National Cancer Institute, CRO-IRCSS, Aviano, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania.
authors.forename: Flavio
authors.initials: F
authors.lastname: Rizzolio
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: 1st Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Barina
authors.affiliation: 1st Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Rajendran
authors.affiliation: Sperimental Oncology, Istituto Oncologico Veneto, IRCCS, Padua, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Microarray Service, Department of Biology, CRIBI Biotechnology Centre, University of Padua, Padua, Italy.
authors.forename: Gerolamo
authors.initials: G
authors.lastname: Lanfranchi
authors.affiliation: 1st Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.affiliation: 1st Surgical Clinic, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy. puc@unipd.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pucciarelli
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000628:therapy*; D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012004:Rectal Neoplasms / Q000235:genetics* / Q000628:therapy*; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger