title: High miR-21 expression from FFPE tissues is associated with poor survival and response to adjuvant chemotherapy in colon cancer.
abstract: Colon cancer (CC) is a leading cause of cancer mortality. Novel biomarkers are needed to identify CC patients at high risk of recurrence and those who may benefit from therapeutic intervention. The aim of this study is to investigate if miR-21 expression from RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue sections is associated with prognosis and therapeutic outcome for patients with CC. The expression of miR-21 was measured by quantitative reverse transcriptase-polymerase chain reaction in a Japanese cohort (stage I-IV, n = 156) and a German cohort (stage II, n = 145). High miR-21 expression in tumors was associated with poor survival in both the stage II/III Japanese (p = 0.0008) and stage II German (p = 0.047) cohorts. These associations were independent of other clinical covariates in multivariable models. Receipt of adjuvant chemotherapy was not beneficial in patients with high miR-21 in either cohort. In the Japanese cohort, high miR-21 expression was significantly associated with poor therapeutic outcome (p = 0.0001) and adjuvant therapy was associated with improved survival in patients with low miR-21 (p = 0.001). These results suggest that miR-21 is a promising biomarker to identify patients with poor prognosis and can be accurately measured in FFPE tissues. The expression of miR-21 may also identify patients who will benefit from adjuvant chemotherapy.
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Anami
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Schetter
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okayama
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Khan
authors.forename: Elise D
authors.initials: ED
authors.lastname: Bowman
authors.forename: Annett
authors.initials: A
authors.lastname: Mueller
authors.forename: Arno
authors.initials: A
authors.lastname: Schad
authors.forename: Manabu
authors.initials: M
authors.lastname: Shimomura
authors.forename: Takao
authors.initials: T
authors.lastname: Hinoi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Masazumi
authors.initials: M
authors.lastname: Okajima
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D005260:Female; D005557:Formaldehyde; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D053842:Microsatellite Instability; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D016612:Paraffin Embedding; D013534:Survival; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D005557:Formaldehyde
keywords: colorectal cancer; microRNA; prognosis