Analysis of the Expression of Repetitive DNA Elements in Osteosarcoma
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Published on: June 16, 2023
Xuan D Ho1,2, Hoang G Nguyen3, Le H Trinh3
1Department of Oncology, College of Medicine and Pharmacy, Hue University, Hue, Vietnam.
Abstract:
Osteosarcoma (OS) is a rare malignant bone tumor. It affects mostly young persons and has poor outcome with the present treatment. No improvement was observed since the introduction of chemotherapy. The better understanding of osteosarcoma development could indicate better management strategy. Repetitive DNA elements were found to play a role in cancer mechanism especially in epithelial tumors but not yet analyzed in osteosarcoma. We conducted the study to analyse the expression profile of repetitive elements (RE) in osteosarcoma. Methods: Fresh bone paired (tumor and normal bone) samples were obtained from excised parts of tumors of 18 patients with osteosarcoma. We performed sequencing of RNA extracted from 36 samples (18 tumor tissues and 18 normal bone for controls), mapped raw reads to the human genome and identified the REs. EdgeR package was used to analyse the difference in expression of REs between osteosarcoma and normal bone. Results: 82 REs were found differentially expressed (FDR < 0.05) between osteosarcoma and normal bone. Out of all significantly changed REs, 35 were upregulated and 47 were downregulated. HERVs (THE1C-int, LTR5, MER57F and MER87B) and satellite elements (HSATII, ALR-alpha) were the most significantly differential expressed elements between osteosarcoma and normal tissues. These results suggest significant impact of REs in the osteosarcoma. The role of REs should be further studied to understand the mechanism they have in the genesis of osteosarcoma.
Insights
Repetitive DNA elements are altered in osteosarcoma, a rare bone cancer. This study identified 82 differentially expressed repetitive elements, offering new insights into osteosarcoma development and potential therapeutic targets.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Osteosarcoma (OS) is a rare bone cancer primarily affecting young individuals with poor treatment outcomes.
- Current chemotherapy has not improved OS survival rates, highlighting the need for novel therapeutic strategies.
- Repetitive DNA elements (REs) are implicated in various cancers, but their role in OS remains under-investigated.
Purpose of the Study:
- To investigate the expression profile of repetitive elements (REs) in osteosarcoma (OS) tissues compared to normal bone.
- To identify specific REs that are differentially expressed in OS and may contribute to its pathogenesis.
Main Methods:
- Paired tumor and normal bone samples from 18 osteosarcoma patients were analyzed.
- RNA sequencing was performed on 36 samples, followed by mapping to the human genome to identify REs.
- Differential expression analysis was conducted using the EdgeR package.
Main Results:
- 82 repetitive elements (REs) showed significant differential expression (FDR < 0.05) between osteosarcoma and normal bone.
- Of these, 35 REs were upregulated and 47 were downregulated in osteosarcoma.
- Human endogenous retroviruses (HERVs) and satellite elements were among the most significantly altered REs.
Conclusions:
- Repetitive DNA elements play a significant role in the molecular landscape of osteosarcoma.
- Further research into the function of these REs is crucial for understanding OS genesis.
- Identifying the specific mechanisms of REs in OS could lead to improved diagnostic and therapeutic approaches.
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