Format

Send to

Choose Destination
Exp Biol Med (Maywood). 2017 Dec;242(18):1802-1811. doi: 10.1177/1535370217736512. Epub 2017 Oct 19.

Whole transcriptome analysis identifies differentially regulated networks between osteosarcoma and normal bone samples.

Author information

1
1 Department of Oncology, 155407 College of Medicine and Pharmacy , Hue University, Hue 53000, Vietnam.
2
2 Department of Pathophysiology, 37546 University of Tartu , Tartu 50411, Estonia.
3
3 Department of Oncology, Hanoi Medical University, Hanoi 15000, Vietnam.
4
4 Department of Reproductive Biology, 85334 Estonian University of Life Sciences , Tartu 51014, Estonia.
5
5 Department of Traumatology and Orthopedics, 37546 University of Tartu , Tartu 50411, Estonia.
6
6 Clinic of Traumatology and Orthopaedics of Tartu University Hospital, Tartu 50406, Estonia.
7
7 Department of Orthopedics, 155407 College of Medicine and Pharmacy , Hue University, Hue 53000, Vietnam.

Abstract

We performed whole transcriptome analysis of osteosarcoma bone samples. Initially, we sequenced total RNA from 36 fresh-frozen samples (18 tumoral bone samples and 18 non-tumoral paired samples) matching in pairs for each osteosarcoma patient. We also performed independent gene expression analysis of formalin-fixed paraffin-embedded samples to verify the RNAseq results. Formalin-fixed paraffin-embedded samples allowed us to analyze the effect of chemotherapy. Data were analyzed with DESeq2, edgeR and Reactome packages of R. We found 5365 genes expressed differentially between the normal bone and osteosarcoma tissues with an FDR below 0.05, of which 3399 genes were upregulated and 1966 were downregulated. Among those genes, BTNL9, MMP14, ABCA10, ACACB, COL11A1, and PKM2 were expressed differentially with the highest significance between tumor and normal bone. Functional annotation with the reactome identified significant changes in the pathways related to the extracellular matrix degradation and collagen biosynthesis. It was suggested that chemotherapy may induce the modification of ECM with important collagen biosynthesis. Taken together, our results indicate that changes in the degradation of extracellular matrix seem to be an important mechanism of osteosarcoma and efficient chemotherapy induces the genes related to bone formation. Impact statement Osteosarcoma is a rare disease but it is of interest to many scientists all over the world because the current standard treatment still has poor results. We sequenced total RNA from 36 fresh-frozen paired samples (18 tumoral bone samples and 18 non-tumoral paired samples) from osteosarcoma patients. We found that differences in the gene expressions between the normal and affected bones reflected the changes in the regulation of the degradation of collagen and extracellular matrix. We believe that these findings contribute to the understanding of OS and suggest ideas for further studies.

KEYWORDS:

Osteosarcoma; RNA sequencing; gene expression profiling; high-through put nucleotide sequencing; osteogenic sarcoma; transcriptome

PMID:
29050494
PMCID:
PMC5714151
DOI:
10.1177/1535370217736512
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center