Open Accessmi RNA profiling identifies deregulated mi RNA s associated with osteosarcoma development and time to metastasis in two large cohorts
Author(s) -
Andersen Gitte B.,
Knudsen Alice,
Hager Henrik,
Hansen Lise L.,
Tost Jörg
Publication year - 2018
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12154
Subject(s) - rna , carcinogenesis , gene expression , microrna , messenger rna , osteosarcoma , biology , cancer research , gene expression profiling , gene , microbiology and biotechnology , genetics
Osteosarcoma ( OS ) is an aggressive bone tumor primarily affecting children and adolescents. The etiology of OS is not fully understood. Thus, there is a great need to obtain a better understanding of OS development and progression. Alterations in mi RNA expression contribute to the required molecular alterations for neoplastic initiation and progression. This study is the first to investigate mi RNA expression in OS in a large discovery and validation cohort comprising a total of 101 OS samples. We established the signature of altered mi RNA expression in OS by profiling the expression level of 752 mi RNA s in 23 OS samples using sensitive LNA ‐enhanced qPCR assays. The identified mi RNA expression changes were correlated with gene expression in the same samples. Furthermore, mi RNA expression changes were validated in a second independent cohort consisting of 78 OS samples. Analysis of 752 mi RNA s in the discovery cohort led to the identification of 33 deregulated mi RNA s in OS . Twenty‐nine mi RNA s were validated with statistical significance in the second cohort comprising 78 OS samples. mi RNA / mRNA targets were determined, and 361 genes with an inverse expression of the target mi RNA were identified. Both the mi RNA s and the identified target genes were associated with multiple pathways related to cancer as well as bone cell biology, thereby correlating the deregulated mi RNA s with OS tumorigenesis. An analysis of the prognostic value of the 29 mi RNA s identified miR‐221/miR‐222 to be significantly associated with time to metastasis in both cohorts. This study contributes to a more profound understanding of OS tumorigenesis, by substantiating the importance of mi RNA deregulation. We have identified and validated 29 deregulated mi RNA s in the – to our knowledge – largest discovery and validation cohorts used so far for mi RNA analyses in OS . Two of the mi RNA s showed a promising potential as prognostic biomarkers for the aggressiveness of OS .