Medical Oncology Department, Institut Paoli-Calmettes, 13009 Marseille, France.
Predictive Oncology Laboratory, Inserm UMR1068, Centre National de la Recherche Scientifique (CNRS) UMR7258, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix-Marseille University U105, 13009 Marseille, France.
Int J Mol Sci. 2024 Nov 7;25(22):11953. doi: 10.3390/ijms252211953.
Antibody-drug conjugates targeting folate receptor alpha (FRα) are a promising treatment for platinum-resistant ovarian cancer (OC) with high FRα expression. Challenges persist in accurately assessing FRα expression levels. Our study aimed to better elucidate FRα gene expression and identify mRNA signatures in OC. We pooled OC gene expression data from 16 public datasets, encompassing 1832 OC and 30 normal ovarian tissues. Additional data included DNA copy number and methylation data from TCGA and protein data from 363 cancer cell lines from the Broad Institute Cancer Cell Line Encyclopedia. mRNA expression was significantly correlated with protein expression in pan-cancer cell lines and ovarian cancer cell lines. expression was higher in OC samples than in normal ovarian tissues (OR = 3.88, = 6.97 × 10). Patients with high expression were more likely to be diagnosed with serous histology, FIGO stage III-IV, and high-grade tumors; however, nearly similar percentages of patients with low expression were also diagnosed with these features. mRNA expression was not correlated with platinum sensitivity or complete surgery, nor with prognosis. However, we identified a 187-gene signature associated with high expression that was significantly associated with improved survival (HR = 0.71, = 1.18 × 10), independently from clinicopathological features. We identified a gene expression signature correlated to high FRα expression and OC prognosis, which may be used to refine therapeutic strategies targeting FRα in OC. These findings warrant validation in larger cohorts.
靶向叶酸受体 alpha（FRα）的抗体药物偶联物是治疗高 FRα 表达的铂耐药卵巢癌（OC）的一种有前途的方法。然而，在准确评估 FRα 表达水平方面仍然存在挑战。我们的研究旨在更好地阐明 FRα 基因表达，并确定 OC 中的 mRNA 特征。我们汇集了来自 16 个公共数据集的 OC 基因表达数据，其中包括 1832 个 OC 和 30 个正常卵巢组织。额外的数据包括 TCGA 的 DNA 拷贝数和甲基化数据以及 Broad Institute Cancer Cell Line Encyclopedia 中的 363 个癌症细胞系的蛋白质数据。在泛癌细胞系和卵巢癌细胞系中，mRNA 表达与蛋白质表达显著相关。在 OC 样本中的表达高于正常卵巢组织（OR=3.88，=6.97×10）。高 表达的患者更有可能被诊断为浆液性组织学、FIGO 分期 III-IV 和高级别肿瘤；然而，低 表达的患者也有相似比例被诊断出具有这些特征。然而，mRNA 表达与铂敏感性或完全手术、预后均无相关性。然而，我们确定了一个与高 表达相关的 187 个基因特征，该特征与改善的生存显著相关（HR=0.71，=1.18×10），独立于临床病理特征。我们确定了一个与 FRα 高表达和 OC 预后相关的基因表达特征，它可能被用于改进针对 OC 中 FRα 的治疗策略。这些发现需要在更大的队列中进行验证。
