title: Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer.
abstract: The role of adjuvant chemotherapy in stage T2-T3N0 colon cancer (CC) is controversial and there are currently no reliable factors allowing for individual selection of patients with high risk of relapse for such therapy. We searched for microRNA-based signature with prognostic significance in this group. We assessed by qRT-PCR expression of 754 microRNAs (miRNAs) in tumour samples from 85 stage pT2-3N0 CC patients treated with surgery alone. MiRNA expression was compared between two groups of patients: 40 and 45 patients who did and did not develop distant metastases after resection, respectively. Additionally, miRNA expression was compared between CC and normal colon mucosa samples and between the mismatch repair (MMR) competent and deficient tumours. Low expression of miR-1300 and miR-939 was significantly correlated with shorter distant metastasis-free survival (DMFS) in Cox univariate analysis (p.adjusted = 0.049). The expression signature of five miRNAs (miR-1296, miR-135b, miR-539, miR-572 and miR-185) was found to be prognostic [p = 1.28E-07, HR 8.4 (95 % CI: 3.81-18.52)] for DMFS and cross-validated in a leave-one-out analysis, with the sensitivity and specificity of 74 and 78 %, respectively. The expression of miR-592 was significantly associated with the MMR status (p.adjusted <0.01). The expression of several novel miRNAs were found to be tumour specific, e.g. miR-888, miR-523, miR-18b, miR-302a, miR-423-5p, miR-582-3p (p < 0.05). We developed a miRNA expression signature that may be predictive for the risk of distant relapse in early stage CC and confirmed previously reported association between miR-592 expression and MMR status.
authors.affiliation: Department of Surgical Oncology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Bobowicz
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdansk, 7 Dębinki St., 80-211, Gdańsk, Poland. mskrzypski@gumed.edu.pl.
authors.forename: Marcin
authors.identifier: 0000-0002-4391-4318
authors.initials: M
authors.lastname: Skrzypski
authors.affiliation: Department of Pathomorfology, Medical University of Gdansk, Gdańsk, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Czapiewski
authors.affiliation: Institute of Automatic Control, Data Mining Group, Silesian University of Technology, Gliwice, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Marczyk
authors.affiliation: Institute of Forensic Medicine, Medical University of Gdansk, Gdańsk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Maciejewska
authors.affiliation: Department and Clinic of Oncologic Surgery, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Jankowski
authors.affiliation: Department of Clinical Oncology, Centre of Oncology, Bydgoszcz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Szulgo-Paczkowska
authors.affiliation: Department and Clinic of Oncologic Surgery, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zegarski
authors.affiliation: Institute of Forensic Medicine, Medical University of Gdansk, Gdańsk, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Pawłowski
authors.affiliation: Institute of Automatic Control, Data Mining Group, Silesian University of Technology, Gliwice, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Polańska
authors.affiliation: Department of Pathomorfology, Medical University of Gdansk, Gdańsk, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.affiliation: Department of Surgical Oncology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Jaśkiewicz
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdansk, 7 Dębinki St., 80-211, Gdańsk, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C000588991:MIRN592 microRNA, human; D035683:MicroRNAs
keywords: colon cancer; metastasis; miR-1300; miR-939; microRNA expression; prognostic marker