title: Tumor microRNA-29a expression and the risk of recurrence in stage II             colon cancer.
abstract: There is emerging evidence for the prognostic role of various microRNA (miRNA) molecules in colon cancer. The aim of this study was therefore to compare the miRNA profiles in the primary tumor of patients with recurrent and non-recurrent colon cancer. The study population included 110 patients, 51 (46%) with stage I and 59 (54%) with stage II disease, who underwent curative colectomies between 1995 and 2005 without adjuvant therapy and for whom reliable miRNA expression data were available. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor samples. Initial profiling, using microarrays, was done in order to identify potential biomarkers of recurrence. The miRNA expression was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 months of surgery (bad prognosis group, n=23, 21%) and those who did not (good prognosis group, n=87, 79%) in the entire group and within each stage. The results showed that in stage I, none of the 903 miRNAs tested showed differential expression between patients with good prognosis compared with those with poor prognosis. In contrast, in stage II, one miRNA, miR-29a, showed a clear differential expression between the groups (p=0.028). High expression of miR-29a was associated with a longer disease-free survival (DFS), on both univariate and multivariate analyses. Using miR-29a, the positive predictive value for non-recurrence was 94% (2 recurrences among 31 patients). The differential expression of miR-29a was verified by qRT-PCR, showing a similar impact of this miR on DFS. In conclusion, this study demonstrated a significant impact of miR-29a on the risk of recurrence in patients with stage II but not in patients with stage I colon cancer. Based on these results, a validation study is planned.
authors.affiliation: Institute of Oncology, Davidoff Center, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. brennerb@clalit.org.il
authors.forename: Alina
authors.initials: A
authors.lastname: Weissmann-Brenner
authors.forename: Michal
authors.initials: M
authors.lastname: Kushnir
authors.forename: Gila
authors.initials: G
authors.lastname: Lithwick Yanai
authors.forename: Ranit
authors.initials: R
authors.lastname: Aharonov
authors.forename: Hadas
authors.initials: H
authors.lastname: Gibori
authors.forename: Ofer
authors.initials: O
authors.lastname: Purim
authors.forename: Yulia
authors.initials: Y
authors.lastname: Kundel
authors.forename: Sara
authors.initials: S
authors.lastname: Morgenstern
authors.forename: Marissa
authors.initials: M
authors.lastname: Halperin
authors.forename: Yaron
authors.initials: Y
authors.lastname: Niv
authors.forename: Baruch
authors.initials: B
authors.lastname: Brenner
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D012680:Sensitivity and Specificity
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs