增加PI3K通路活性与21基因复发得分低和中等的患者的乳腺癌复发有关
Lawrence Hsu Lin1, Yvonne Wesseling-Rozendaal2, Varshini Vasudevaraja1
1Department of Pathology, New York University Langone Health and Grossman School of Medicine, New York, New York, USA.
增加PI3K通路活性,而不是PIK3CA突变,可能预测早期乳腺癌复发的21基因复发得分低或中等. 这一发现有助于识别高风险患者,以便制定更好的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 低或中等21基因复发分数 (RS) 的早期乳腺癌对预测复发风险构成挑战.
- 在这个患者群体中确定复发的分子驱动因素对于个性化治疗至关重要.
研究的目的:
- 研究关键信号通路 (ER,AR,PI3K,MAPK) 的活性和早期乳腺癌的突变状态.
- 确定可预测低和中等21基因RS患者复发的分子特征.
主要方法:
- 对18名复发性乳腺癌患者和15名非复发性乳腺癌患者进行了回顾性病例控制研究,这些患者具有低/中等21基因RS.
- 使用qPCR评估ER,AR,PI3K和MAPK通路的mRNA表达.
- 通过向DNA测序分析瘤突变格局.
主要成果:
- 在复发病例 (p=0.0014) 和预测复发 (AUC=0.79) 中,PI3K通路活性显著增加.
- 没有观察到ER,AR或MAPK通路活性的显著差异.
- PIK3CA突变很常见,但与复发或PI3K通路活性无关;较高的Ki67表达与复发相关 (p=0.042).
结论:
- 独立于PIK3CA突变的PI3K通路活性增加可能会导致低/中级21基因RS的早期乳腺癌复发.
- 途径分析,特别是PI3K活性,可以帮助识别这个子组内的高风险患者.
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