Τίτλος:
Direct comparison of metastasis-related miRNAs expression levels in circulating tumor cells, corresponding plasma, and primary tumors of breast cancer patients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
BACKGROUND: Circulating tumor cells (CTCs) and microRNAs (miRNAs) are important in liquid biopsies in which peripheral blood is used to characterize the evolution of solid tumors. We evaluated the expression levels of miR-21, miR-146a, miR-200c, and miR-210 in CTCs of breast cancer patients with verified metastasis and compared their expression levels in corresponding plasma and primary tumors. METHODS: Expression levels of the miRNAs were quantified by quantitative reverse transcription PCR (RTqPCR) in (a) 89 primary breast tumors and 30 noncancerous breast tissues and (b) CTCs and corresponding plasma of 55 patients with metastatic breast cancer and 20 healthy donors. For 30 of these patients, CTCs, corresponding plasma, and primary tumor tissues were available. RESULTS: In formalin-fixed, paraffin-embedded tissues, these miRNAs were differentially expressed between primary breast tumors and noncancerous breast tissues. miR-21 (P < 0.001) and miR-146a (P = 0.001) were overexpressed, whereas miR-200c (P = 0.004) and miR- 210 (P = 0.002) were underexpressed. In multivariate analysis, miR-146a overexpression was significantly [hazard ratio 2.969 (1.231-7.157), P = 0.015] associated with progression-free survival. In peripheral blood, all miRNAs studied were overexpressed in both CTC and corresponding plasma. There was a significant association between miR-21 expression levels in CTCs and plasma for 36 of 55 samples (P = 0.008). In plasma, ROC curve analysis revealed that miR-21, miR-146a, and miR-210 could discriminate patients from healthy individuals. CONCLUSIONS: Metastasis-related miRNAs are overexpressed in CTCs and corresponding plasma; miR-21 expression levels highly correlate in CTCs and plasma; and miR-21, miR-146a, and miR-210 are valuable plasma biomarkers for discriminating patients from healthy individuals. © 2016 American Association for Clinical Chemistry.
Συγγραφείς:
Markou, A.
Zavridou, M.
Sourvinou, I.
Yousef, G.
Kounelis, S.
Malamos, N.
Georgoulias, V.
Lianidou, E.
Περιοδικό:
Advances in Clinical Chemistry
Εκδότης:
American Association for Clinical Chemistry Inc.
Λέξεις-κλειδιά:
epithelial cell adhesion molecule; microRNA 146a; microRNA 200c; microRNA 21; microRNA 210; microRNA, Article; biopsy technique; blood sampling; breast biopsy; breast cancer; cancer patient; circulating tumor cell; controlled study; disease free interval; female; human; human cell; human tissue; liquid biopsy; major clinical study; metastasis; overall survival; peripheral blood mononuclear cell; primary tumor; progression free survival; protein expression; blood; breast tumor; comparative study; gene expression profiling; gene expression regulation; genetics; metabolism; pathology; reverse transcription polymerase chain reaction; tumor embolism, Breast Neoplasms; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplastic Cells, Circulating; Reverse Transcriptase Polymerase Chain Reaction
DOI:
10.1373/clinchem.2015.253716
