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A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
A Transient Receptor Potential-related Gene Model for the Prognostic Assessment and Drug Sensitivity Prediction in
Xiangming Li1, Minghang Zhang2, Ziyi Xu2
1Department of Orthopedics, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, China.
Introduction:
The current study investigated the correlation between Transient Receptor Potential (TRP)-related Genes (TRGs), prognosis, and drug sensitivity in Osteosarcoma (OS).
Methods:
Data from the TARGET-OS and GSE21257 were analyzed for Single-Sample Gene Set Enrichment Analysis (ssGSEA) and Weighted Gene Co-expression Network Analysis (WGCNA). Based on the results from functional enrichment analysis, prognostic genes were selected to construct a RiskScore model, followed by survival analysis and drug-sensitivity prediction. To validate gene function in vitro, we established siRNA-mediated knockdown and overexpression of MYC and PCDHB6 in cell models, followed by rescue experiments and a series of functional assays in OS cell lines.
Results:
Patients with a low TRP score tended to develop metastasis. The high TRP-score group was enriched in complement, interferon_alpha_response, KRAS_signaling_up, inflammatory_response, MYC_target_V2, myogenesis, and G2M_checkpoint. WGCNA identified the green module as a key module, in which a total of 840 modular genes affected OS progression via immune- and pH-related pathways. Five key genes (APBB1IP, CYFIP1, LASP1, MYC, and PCDHB6) were selected to develop a robust prognostic model. MYC knockdown and PCDHB6 overexpression suppressed the migration and invasion of OS cells, and rescue experiments further confirmed their regulatory effects. The high-risk group was enriched in cell cycle and ribosome, while the low-risk group was enriched in complement and coagulation cascades, lysosome, and phagosome. RiskScore was positively correlated with the IC50 of erlotinib, bleomycin, and bortezomib, and negatively correlated with that of VX-680.
Discussion:
This study constructed a five-gene TRP-related prognostic model for OS with strong predictive performance, revealing distinct pathway enrichment and drug sensitivity between the two risk groups.
Conclusion:
The TRG-related gene model may assist in the prediction of prognosis and drug sensitivity in OS, thereby contributing to the development of relevant therapies.
