文章：

南非地区独特的基因表达谱与常规骨肉瘤化疗反应差异相关

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

原文发布日期：23 September 2024

DOI: 10.3390/cancers16183240

类型: Article

开放获取: 是

英文摘要：

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−∆∆CTmethod to determine the fold change in gene expression alongside GAPDH (housekeeping gene). Results: We observed a significant downregulation in the mRNA expression profiles ofABCB1-p-glycoprotein(p= 0.0007),ABCC3(p= 0.002),ERCC1(p= 0.007),p-53(p= 0.007), andRFC1(p= 0.003) in the COS patients compared to the healthy donors. Furthermore,ABCB1-p-glycoprotein(p= 0.008) andABCC3(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 comprisedERCC1[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.

摘要翻译： 

背景：本研究旨在确定南非地区常规骨肉瘤（COS）中与化疗反应相关的预测性基因表达谱。材料与方法：对28例患者进行RNA提取、cDNA合成，并采用RT-PCR 2−∆∆CT法以GAPDH（内参基因）为参照进行基因表达倍比变化的定量分析。结果：与健康供体相比，COS患者中ABCB1-p-糖蛋白（p=0.0007）、ABCC3（p=0.002）、ERCC1（p=0.007）、p-53（p=0.007）及RFC1（p=0.003）的mRNA表达谱均呈现显著下调。进一步分析显示，与健康供体相比，COS肿瘤组织中ABCB1-p-糖蛋白（p=0.008）和ABCC3（p=0.020）亦存在显著下调。单因素逻辑回归分析显示，化疗反应的预测因子包括：ERCC1[限制性立方样条（RCS）节点：OR -0.27；CI -0.504至-0.032；p=0.036]；成骨细胞亚型[OR -0.36；CI -0.652至-0.092；p=0.026]；成纤维细胞亚型[OR 0.91；CI 0.569至1.248；p<0.001]；混合亚型[OR 0.53；CI 0.232至0.032；p=0.032]。多因素逻辑回归分析显示，化疗反应的显著预测因子包括：年龄[RCS节点：OR -2.5；CI -3.616至-1.378；p=0.022]；ABCC3[RCS节点：OR 0.67；CI 0.407至0.936；p=0.016]；ERCC1[RCS节点：OR 0.57；CI 0.235至0.901；p=0.044]；RFC1[RCS节点：OR -1.04；CI -1.592至-0.487；p=0.035]；软骨母细胞亚型[OR -0.83；CI -1.106至-0.520；p=0.012]；成骨细胞亚型[OR -1.28；CI -1.664至-0.901；p=0.007]。结论：在南非人群中，我们观察到骨肉瘤肿瘤发生及化疗反应的特异性基因表达谱，这些发现可能为预后评估和治疗靶点选择提供依据。未来需要在非洲大陆开展更大规模的研究。

原文链接：

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