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Updated: Jun 11, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Unique Gene Expression Profiles within South Africa Are Associated with Varied Chemotherapeutic Responses in
Phakamani G Mthethwa1, Thilona Arumugam2, Veron Ramsuran2
1Dr Pixley Ka Isaka Seme Memorial Hospital, University of KwaZulu-Natal, Nelson Mandela School of Clinical Medicine, 310 Bhejane Street, KwaMashu, Durban 4360, South Africa.
Background:
We determined the predictive gene expression profiles associated with chemo-response in conventional osteosarcomas (COS) within South Africa.
Materials And Methods:
In 28 patients, we performed an RNA extraction, cDNA synthesis, and quantitative analysis using the RT-PCR 2-∆∆CT method to determine the fold change in gene expression alongside GAPDH (housekeeping gene).
Results:
We observed a significant downregulation in the mRNA expression profiles of ABCB1-p-glycoprotein (p = 0.0007), ABCC3 (p = 0.002), ERCC1 (p = 0.007), p-53 (p = 0.007), and RFC1 (p = 0.003) in the COS patients compared to the healthy donors. Furthermore, ABCB1-p-glycoprotein (p = 0.008) and ABCC3 (p = 0.020) exhibited a significant downregulation in the COS tumour tissues when compared to the healthy donors. In our univariate logistic regression, the predictors of chemotherapeutic response comprised ERCC1 [restricted cubic spline (RCS) knot: OR -0.27; CI -0.504 to -0.032; p = 0.036]; osteoblastic subtype [OR -0.36; CI -0.652 to -0.092; p = 0.026); fibroblastic subtype [OR 0.91; CI 0.569 to 1.248; p < 0.001]; and mixed subtype [OR 0.53; CI 0.232 to 0.032; p = 0.032]. In our multivariable logistic regression, the significant predictors of chemotherapeutic response comprised age [RCS knot: OR -2.5; CI -3.616 to -1.378; p = 0.022]; ABCC3 [RCS knot: OR 0.67; CI 0.407 to 0.936, p = 0.016]; ERCC1 [RCS knot: OR 0.57; CI 0.235 to 0.901; p = 0.044]; RFC1 [RCS knot: OR -1.04; CI -1.592 to -0.487; p = 0.035]; chondroblastic subtype [OR -0.83; CI -1.106 to -0.520; p = 0.012]; and osteoblastic subtype [OR -1.28; CI -1.664 to -0.901; p = 0.007].
Conclusions:
In this South African cohort, we observed the unique gene expression profiles of osteosarcoma tumourigenesis and chemotherapeutic responses. These may serve as prognostication and therapeutic targets. Larger-scale research is needed on the African continent.
