Abstract：
Ovarian cancer (OC) ranks among the prevalent tumors affecting the female reproductive system. The aim of this study was to evaluate mitochondria-associated platinum resistance genes using organoid models. Univariate Cox regression, LASSO and multivariate Cox regression analyses were performed on The Cancer Genome Atlas (TCGA) database to construct 2-gene prognostic signature (MUL1 and SSBP1), and GSE26712 dataset was used for external validation. In addition, the relationship between MUL1 and platinum resistance was examined by organoid culture, lentiviral transduction, CCK8 assay, and Western blot. The results showed that patients in the high-risk group exhibited significantly worse OS (P = 0.002, P = 0.017). Drug sensitivity analysis revealed that platinum resistance increased with the upregulation of MUL1 expression (Cor = 0.5154, P = 0.02). Our experimental findings demonstrated that knockout of the MUL1 gene significantly increased apoptosis and enhanced the sensitivity of the OC cell line A2780 to cisplatin. Through this study, we have provided strong evidence for further research on prognostic risk factors and individualized treatment in OC patients, and provided new insights into addressing platinum resistance in OC.
摘要：
卵巢癌（OC）是影响女性生殖系统的常见肿瘤之一。这项研究的目的是使用类器官模型评估线粒体相关的铂抗性基因。单变量Cox回归，在癌症基因组图谱（TCGA）数据库上进行LASSO和多变量Cox回归分析，以构建2基因预后标签（MUL1和SSBP1），和GSE26712数据集用于外部验证。此外,通过类器官培养检查MUL1和铂抗性之间的关系，慢病毒转导，CCK8测定，和Westernblot。结果显示，高危组患者的OS显著恶化（P=0.002，P=0.017）。药物敏感性分析显示铂类耐药随MUL1表达上调而增加(Cor=0.5154,P=0.02)。我们的实验发现表明，MUL1基因的敲除显着增加了细胞凋亡，并增强了OC细胞系A2780对顺铂的敏感性。通过这项研究,我们为进一步研究OC患者的预后危险因素和个体化治疗提供了有力的证据,并为解决OC中的铂电阻提供了新的见解。
