在临床前研究中，p53 功能丧失会影响化疗反应，但这尚未得到一致的临床验证。我们在 TCGA 中训练了来自泛癌临床样本的 TP53 丢失表型基因表达特征。在体外，TP53 缺失表型特征可预测跨癌症类型的化疗反应。在接受新辅助化疗治疗的 3003 例乳腺癌样本的临床数据集中，TP53 缺失表型样本获得病理完全缓解 (pCR) 的可能性高出 56%，在 ER 阳性的患者中，TP53 缺失表型与 pCR 之间存在显着相关性。和 ER 阴性肿瘤。在 I-SPY2 试验的独立临床验证中 (N = 987)，我们证实了与新辅助化疗 pCR 的相关性，并发现与非 TP53 丢失表型肿瘤相比，TP53 丢失表型肿瘤的化学免疫治疗反应率更高 (64% vs. 28%）。 TP53 丢失表型特征可以预测体外各种癌症类型的化疗反应，并且在概念验证临床验证中与多个临床乳腺癌队列的新辅助化疗反应相关。© 2024。这是美国政府的工作，不属于美国政府的工作。美国的版权保护；可能适用外国版权保护。

In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types. In a clinical dataset of 3003 breast cancer samples treated with neoadjuvant chemotherapy, the TP53-loss phenocopy samples were 56% more likely to have a pathologic complete response (pCR), with a significant association between TP53-loss phenocopy and pCR in both ER positive and ER negative tumors. In an independent clinical validation in the I-SPY2 trial (N = 987), we confirmed the association with neoadjuvant chemotherapy pCR and found higher rates of chemoimmunotherapy response in TP53-loss phenocopy tumors compared to non-TP53-loss phenocopy tumors (64% vs. 28%). The TP53-loss phenocopy signature predicts chemotherapy response across cancer types in vitro, and in a proof-of-concept clinical validation is associated with neoadjuvant chemotherapy response across multiple clinical breast cancer cohorts.© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.