title: Assessing the clinical value of microRNAs in formalin-fixed paraffin-embedded liposarcoma tissues: Overexpressed miR-155 is an indicator of poor prognosis.
abstract: Liposarcoma (LPS) is a malignancy with extreme heterogeneity and thus optimization towards personalizing patient prognosis and treatment is essential. Here, we evaluated miR-155, miR-21, miR-143, miR-145 and miR-451 that are implicated in LPS, as novel FFPE tissue biomarkers.A total of 83 FFPE tissue specimens from primary LPS and lipomas (LPM) were analyzed. A proteinase K incubation-Trizol treatment coupled protocol was used for RNA isolation. After polyadenylation of total RNA and reverse transcription, expression analysis of 9 candidate reference and 5 target miRNAs was performed by qPCR. Genorm and NormFinder were used for finding the most suitable molecules for normalization. Survival analyses were performed in order to evaluate the prognostic potential of miRNAs.MiR-103 and miR-191 are most suitable for normalization of miRNA expression in LPS. MiR-155 and miR-21 are clearly overexpressed (P<0.001) in LPS compared with LPM specimens, whereas miR-145 (P<0.001), miR-143 (P =0.008) and miR-451 (P=0.037) are underexpressed. MiR-155 (P=0.007) and miR-21 (P=0.029) are differentially expressed between well-differentiated, dedifferentiated, myxoid/round cell and pleomorphic LPs tumor subtypes. MiR-155 represents a novel independent indicator of unfavorable prognosis in LPS (HR = 2.97, 95% CI = 1.23-7.17, P = 0.016).
authors.affiliation: Cancer Biobank Center, University of Ioannina, University Campus, Ioannina, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kapodistrias
authors.affiliation: Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mavridis
authors.affiliation: Department of Pathology, School of Medicine, University of Ioannina, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Batistatou
authors.affiliation: Clinical Oncology Department, Norwich University Hospital, UK.
authors.forename: Penelope
authors.initials: P
authors.lastname: Gogou
authors.affiliation: London Sarcoma Service, Department of Oncology, UCLH, London, UK.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Karavasilis
authors.affiliation: Cancer Biobank Center, University of Ioannina, University Campus, Ioannina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Sainis
authors.affiliation: Cancer Biobank Center, University of Ioannina, University Campus, Ioannina, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Briasoulis
authors.affiliation: Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005404:Fixatives / Q000737:chemistry*; D005557:Formaldehyde / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008067:Lipoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008080:Liposarcoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016707:Tissue Fixation / Q000379:methods*; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D005404:Fixatives; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D005557:Formaldehyde
keywords: liposarcoma; miR-155; miRNA expression normalization; miRNAs; prognostic biomarker