改善基因和转移性疾病预测的生物标志物:从前性研究的见解
Tom Drossart1, Alexandre Buffet1,2, Ali Janbain3
1Université Paris Cité, Inserm, PARCC, Équipe Labellisée Ligue contre le Cancer, F-75015 Paris, France.
The Journal of clinical endocrinology and metabolism
|November 14, 2024
概括
像血糖酸盐和循环miR-483-5p这样的生物标志物可以帮助识别 paraganglioma 和 pheochromocytoma (PPGL) 的遗传状态和恶性瘤风险. 将这些生物标志物与临床数据相结合,为转移PPGL患者提供了高准确度.
科学领域:
- 内分泌学和瘤学的内分泌学和瘤学.
- 遗传学和基因组学 遗传学和基因组学
- 生物标志物发现发现
背景情况:
- 准确的风险分层对 paraganglioma 和 pheochromocytoma (PPGL) 对于患者管理至关重要.
- 区分良性和恶性PPGL,并识别特定的遗传变化,仍然是一个临床挑战.
研究的目的:
- 评估基因组,代谢组和组织病理学生物标志物的诊断准确性,以预测PPGL中的转移潜力和遗传状态.
- 评估新生物标志物的实用性与PPGL风险分层的既定方法相结合.
主要方法:
- 一项前性研究 (COMETE-TACTIC) 涉及16个转诊中心的231名PPGL患者.
- 使用下一代测序 (NGS),免疫组织化学 (SDHB,SDHA,CA9),热测序 (TERT促进物甲基化),气色谱-MS/MS (代谢学) 和滴滴数字PCR (循环miRNA) 分析瘤组织和液体活检.
主要成果:
- 瘤分析优于生殖线分析来确定遗传状态.
- 血中酸盐水平和TERT促进物甲基化在预测SDHx突变和转移状态方面显示出显著的准确性.
- 循环中的miR-483-5p被确定为转移性PPGL的关键分类因子. 组合生物标志物实现了对转移潜力的高诊断准确性 (AUC-ROC 0.93).
结论:
- 循环中的miR-483-5p,血糖酸盐,TERT促进物甲基化和SDHB免疫染色是PPGL风险分层的宝贵工具.
- 这些生物标志物与临床数据的整合显著提高了转移性PPGL的诊断准确性,达到0.97.9的AUC-ROC.
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