由 ABCB1 基因编码的药物外排转运蛋白 P-糖蛋白可促进获得性化疗耐药。我们使用数字液滴 PCR 探索了卵巢癌患者（来自 79 名癌症患者的 173 份纵向血清样本）中循环无细胞 ABCB1 转录物 (cfABCB1tx) 的存在和临床相关性。 cfABCB1tx 在初步诊断时很容易检测到（中位 354 mRNA 拷贝/20 µl 血清），与FIGO 阶段和预测的手术结果平行（分别为 p = 0.023，p=0.022）。初次诊断时 cfABCB1tx 水平升高表明 PFS (HR = 2.329, 95%CI:1.374-3.947, p = 0.0017) 和 OS (HR = 2.074, 95%CI:1.194-3.601, p = 0.0096) 较差。铂类化疗下的 cfABCB1tx 诱导是 OS 较差的独立预测因子（HR = 2.597，95%CI：1.218-5.538，p = 0.013），并且与骨髓中存在播散性肿瘤细胞形成的微转移表型平行。我们观察到 cfABCB1tx 与转移诱导子 MACC1（ABCB1 的转录激活子）的循环转录物之间存在很强的相关性。对 cfABCB1tx 和循环无细胞 MACC1 转录本 (cfMACC1tx) 的综合评估改善了预后预测，其中 cfABCB1tx-high/cfMACC1tx-high 表型具有最高的复发和死亡风险。最后，我们提供了原理证明，即 ABCB1 转录本在卵巢癌患者的液体活检中很容易追踪，为系统监测 ABCB1/P-糖蛋白表达动态开辟了新的维度。© 2024。作者。

The drug efflux transporter P-glycoprotein, encoded by the ABCB1 gene, promotes acquired chemoresistance. We explored the presence and clinical relevance of circulating cell-free ABCB1 transcripts (cfABCB1tx) in ovarian cancer patients (173 longitudinal serum samples from 79 cancer patients) using digital droplet PCR. cfABCB1tx were readily detectable at primary diagnosis (median 354 mRNA copies/20 µl serum), paralleled FIGO-stage and predicted surgical outcome (p = 0.023, p=0.022, respectively). Increased cfABCB1tx levels at primary diagnosis indicated poor PFS (HR = 2.329, 95%CI:1.374-3.947, p = 0.0017) and OS (HR = 2.074, 95%CI:1.194-3.601, p = 0.0096). cfABCB1tx induction under platinum-based chemotherapy was an independent predictor for poor OS (HR = 2.597, 95%CI: 1.218-5.538, p = 0.013) and paralelled a micrometastatic phenotype, shaped by the presence of disseminated tumor cells in the bone marrow. A strong correlation was observed between cfABCB1tx and circulating transcripts of the metastasis-inducer MACC1, which is the transcriptional activator of ABCB1. Combined assessment of cfABCB1tx and circulating cell-free MACC1 transcripts (cfMACC1tx) resulted in an improved prognostic prediction, with  the cfABCB1tx-high/cfMACC1tx-high phenotype bearing the highest risk for relapse and death. Conclusively, we provide proof of principle, that ABCB1 transcripts are readily traceable in the liquid-biopsy of ovarian cancer patients, advancing a new dimension for systemic monitoring of ABCB1/P-glycoprotein expression dynamics.© 2024. The Author(s).