Mthethwa Phakamani G, Arumugam Thilona, Ramsuran Veron, Gokul Anmol, Rodseth Reitze, Marais Leonard
Dr Pixley Ka Isaka Seme Memorial Hospital, University of KwaZulu-Natal, Nelson Mandela School of Clinical Medicine, 310 Bhejane Street, KwaMashu, Durban 4360, South Africa.
Centre for the AIDS Programme of Research in South Africa (CAPRISA), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa.
Cancers (Basel). 2024 Sep 23;16(18):3240. doi: 10.3390/cancers16183240.
We determined the predictive gene expression profiles associated with chemo-response in conventional osteosarcomas (COS) within South Africa.
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).
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].
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.
我们确定了与南非传统骨肉瘤（COS）化疗反应相关的预测性基因表达谱。
对28例患者进行RNA提取、cDNA合成，并使用RT-PCR 2方法进行定量分析，以确定与甘油醛-3-磷酸脱氢酶（管家基因）相比基因表达的倍数变化。
与健康供体相比，我们观察到COS患者中（ = 0.0007）、（ = 0.002）、（ = 0.007）、（ = 0.007）和（ = 0.003）的mRNA表达谱显著下调。此外，与健康供体相比，（ = 0.008）和（ = 0.020）在COS肿瘤组织中表现出显著下调。在我们的单变量逻辑回归中，化疗反应的预测因素包括 [受限立方样条（RCS）节点：OR -0.27；CI -0.504至-0.032； = 0.036]；成骨细胞亚型 [OR -0.36；CI -0.652至-0.092； = 0.026]；纤维母细胞亚型 [OR 0.91；CI 0.569至1.248； < 0.001]；以及混合亚型 [OR 0.53；CI 0.232至0.032； = 0.032]。在我们的多变量逻辑回归中，化疗反应的显著预测因素包括年龄 [RCS节点：OR -2.5；CI -3.616至-1.378； = 0.022]；[RCS节点：OR 0.67；CI 0.407至0.936， = 0.016]；[RCS节点：OR 0.57；CI 0.235至0.901； = 0.044]；[RCS节点：OR -1.04；CI -1.592至-0.487； = 0.035]；软骨母细胞亚型 [OR -0.83；CI -1.106至-0.520； = 0.012]；和成骨细胞亚型 [OR -1.28；CI -1.664至-0.901； = 0.007]。
在这个南非队列中，我们观察到骨肉瘤肿瘤发生和化疗反应的独特基因表达谱。这些可能作为预后和治疗靶点。非洲大陆需要进行更大规模的研究。
