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).
Highlights
Liposarcoma (LPS) accounts for at least 20% of total soft tissue sarcomas cases [1, 2]
The combination of miR-103 and miR-191 levels is suitable for normalization of miRNA expression in liposarcoma
Individuals with distinct pathobiological features are erroneously categorized in the same prognostic www.impactjournals.com/oncotarget group without taking into account the heterogeneity in the underlying molecular mechanisms that drive liposarcomatogenensis [2, 4, 7]
Summary
Liposarcoma (LPS) accounts for at least 20% of total soft tissue sarcomas cases [1, 2]. It is subdivided into four histologic subtypes forming three biologic groups with distinct morphological and cytogenetic characteristics: i) well-differentiated/ de-differentiated (WDLPS/DDLPS) with amplification of chromosome 12q13-1 resulting to MDM2, HMGA2 and CDK4 overexpression, ii) myxoid/round cell (MRC) LPS with translocation t(12;16)(q13;p11.2) leading to a uniquely aberrant transcription factor derived from FUS-CHOP fusion and iii) pleomorphic LPS, a high-grade, rare and aggressive disease variant [1,2,3]. Guidelines for adjuvant and neoadjuvant therapy and the assessment of LPS histologic subtype fluctuate greatly, even among major sarcoma centers. The identification of novel prognostic biomarkers is necessary and could help towards the stratification of patients into those who will benefit from (neo)adjuvant treatment, and those who can be spared from the harmful side-effects of cytotoxic therapy and can follow a monitoring approach [1, 7,8,9,10]
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