title: Plasma microRNAs predicting clinical outcome in metastatic colorectal cancer patients receiving first-line oxaliplatin-based treatment.
abstract: The conventional first-line chemotherapy for metastatic colorectal cancer (mCRC) consists of fluorouracil (5-FU) in combination with either oxaliplatin or irinotecan. We have explored microRNAs (miRNAs) in plasma as potential predictive markers to oxaliplatin-based chemotherapy. The expression of 742 miRNAs was examined in plasma samples from 24 mCRC patients (12 responders and 12 non-responders) before onset and after four cycles of 5-FU/oxaliplatin. The top differentially expressed miRNAs between responders and non-responders were selected for further analysis in a validation cohort of 150 patients. In the validation cohort, there was a significant overrepresentation of miRNAs with higher mean expression in the non-responder group than in the responder group before treatment (p < 0.002). Moreover, we found three miRNAs (miR-106a, miR-484, and miR-130b) to be significantly differentially expressed before treatment (p = 0.008, 0.008, and 0.008, respectively). All three miRNAs were upregulated in non-responders. High expression of miR-27b, miR-148a, and miR-326 were associated with decreased progression-free survival (Hazard ratios (HR) of 1.4 (95% CI 1.1-1.8, p = 0.004), 1.3 (95% CI 1.1-1.6, p = 0.007), and 1.4 (95% CI 1.1-1.8, p = 0.008), respectively). miR-326 was also associated with decreased overall survival (HR 1.5 (95% CI 1.1-2.0, p = 0.003)). There were no significantly differentially expressed miRNAs in association with clinical outcome after four cycles of chemotherapy. The present study demonstrates that plasma miRNAs analyzed before treatment may serve as non-invasive markers predicting outcome in mCRC patients treated with 5-FU and oxaliplatin-based chemotherapy.
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Ullernchauseen 70, 0310 Oslo, Norway.
authors.forename: J B
authors.initials: JB
authors.lastname: Kjersem
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Ikdahl
authors.affiliation: Biomedical Research Group, Department of Informatics, University of Oslo, Norway; Center for Cancer Biomedicine, University of Oslo, Norway.
authors.forename: O C
authors.initials: OC
authors.lastname: Lingjaerde
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Guren
authors.affiliation: Department of Oncology, Oslo University Hospital, Oslo, Norway.
authors.forename: K M
authors.initials: KM
authors.lastname: Tveit
authors.affiliation: Department of Genetics, Institute for Cancer Research, Oslo University Hospital, Ullernchauseen 70, 0310 Oslo, Norway. Electronic address: elin.kure@rr-research.no.
authors.forename: E H
authors.initials: EH
authors.lastname: Kure
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015331:Cohort Studies; D003106:Colon / Q000187:drug effects / Q000473:pathology; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000077146:Irinotecan; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000077150:Oxaliplatin; D011379:Prognosis; D012007:Rectum / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin
keywords: 5-Fluorouracil; Circulating microrna; Metastatic colorectal cancer; Oxaliplatin; Predictive markers