研究动态
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基于癌症基因组图谱分析的高级别浆膜性卵巢癌(HGSOC)中的癌症干细胞标记物的临床相关性和预后价值。

Cancer Stem Cell Markers-Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis.

发表日期:2023 Aug 13
作者: Natalia Iżycka, Mikołaj Piotr Zaborowski, Łukasz Ciecierski, Kamila Jaz, Sebastian Szubert, Cezary Miedziarek, Marta Rezler, Kinga Piątek-Bajan, Aneta Synakiewicz, Anna Jankowska, Marek Figlerowicz, Karolina Sterzyńska, Ewa Nowak-Markwitz
来源: Stem Cell Research & Therapy

摘要:

癌干细胞(CSCs)可能增加卵巢癌(OC)复发风险。进一步的研究需要更确切地确定CSC标记物与OC患者的临床结果之间是否存在关联。如果证明正确,CSC标记物未来可以用于帮助预测生存并指示新的治疗靶点。本研究旨在确定高级浆液性卵巢癌(HGSOC)中的CSC标记物在mRNA和蛋白质水平上的表达,并研究它们与临床表现、疗效和复发风险的关联。我们利用The Cancer Genome Atlas(TCGA)数据库中的558个卵巢癌肿瘤样本评估13个CSC标记物(ALDH1A1、CD44、EPCAM、KIT、LGR5、NES、NOTCH3、POU5F1、PROM1、PTTG1、ROR1、SOX9和THY1)。通过微阵列和质谱仪评估的mRNA和蛋白质水平数据从TCGA中提取。我们使用包括流行病学数据、表达水平和机器学习方法的多个变量建立了预测化疗反应和生存的模型。ALDH1A1和LGR5的mRNA表达表明对铂类药物敏感性更高(p = 3.50 × 10-3;p = 0.01,分别)。POU5F1的mRNA表达标记具有铂类药物抗性的肿瘤(p = 9.43 × 10-3)。CD44和EPCAM的mRNA表达与较长的总体生存期(OS)呈相关性(p = 0.043;p = 0.039,分别)。THY1的mRNA和蛋白质水平与较差的OS相关(p = 0.019;p = 0.015,分别)。EPCAM(p = 0.004)、LGR5(p = 0.018)和CD44(p = 0.012)对无病生存期(DFS)产生积极影响。在基于CSC标记物表达的多元模型中,高风险组的中位数总体生存期比低风险组长9.1个月(p < 0.001)。OC中的ALDH1A1、CD44、EPCAM、LGR5、POU5F1和THY1水平可能作为预后因素用于预测主要结果并帮助预测治疗反应。
Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients' clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10-3; p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10-3). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response.