Unique Gene Expression Profiles within South Africa Are Associated with Varied Chemotherapeutic Responses in Conventional Osteosarcoma.

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 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 ( = 0.0007), ( = 0.002), ( = 0.007), ( = 0.007), and ( = 0.003) in the COS patients compared to the healthy donors. Furthermore, ( = 0.008) and ( = 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 [restricted cubic spline (RCS) knot: OR -0.27; CI -0.504 to -0.032; = 0.036]; osteoblastic subtype [OR -0.36; CI -0.652 to -0.092; = 0.026); fibroblastic subtype [OR 0.91; CI 0.569 to 1.248; < 0.001]; and mixed subtype [OR 0.53; CI 0.232 to 0.032; = 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; = 0.022]; [RCS knot: OR 0.67; CI 0.407 to 0.936, = 0.016]; [RCS knot: OR 0.57; CI 0.235 to 0.901; = 0.044]; [RCS knot: OR -1.04; CI -1.592 to -0.487; = 0.035]; chondroblastic subtype [OR -0.83; CI -1.106 to -0.520; = 0.012]; and osteoblastic subtype [OR -1.28; CI -1.664 to -0.901; = 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.