Nanomechanical biomarkers of single circulating tumor cells for detection of castration resistant prostate cancer.

Emerging evidence shows that nanomechanical phenotypes of circulating tumor cells (CTC) could become potential biomarkers for metastatic castration resistant prostate cancer (mCRPC). To determine the nanomechanical phenotype of CTCs we applied atomic force microscopy (AFM) employing the PeakForce quantitative nanomechanical (QNM) imaging. We assessed biophysical parameters (elasticity, deformation and adhesion) of 130 CTCs isolated from blood samples from 5 castration sensitive (CS) and 12 castration resistant prostate cancer (CRPCa) patients. We found that CTCs from CRPCa patients are 3 times softer, 3 times more deformable and 7 times more adhesive than counterparts from CSPCa patients. Both nonsupervised hierarchical clustering and principle component analysis show that three combined nanomechanical parameters could constitute a valuable set to distinguish between CSPCa and CRPCa. Our study indicates that nanomechanical phenotypes of CTCs may serve as novel and effective biomarkers for mCRPC.

新出现的证据表明，循环肿瘤细胞（CTC）的纳米力学表型可能成为转移性去势抵抗性前列腺癌（mCRPC）的潜在生物标志物。 为了确定CTC的纳米力学表型，我们应用了原子力显微镜（AFM），采用PeakForce定量纳米力学（QNM）成像技术。我们评估了从5名去势敏感（CS）和12名去势抵抗性前列腺癌（CRPCa）患者的血液样本中分离出的130个CTC的生物物理参数（弹性、变形和黏附性）。 我们发现，来自CRPCa患者的CTC比来自CSPCa患者的CTC软3倍，变形能力强3倍，黏附性强7倍。无监督层次聚类和主成分分析均表明，三个组合的纳米力学参数可构成一组有价值的数据，用于区分CSPCa和CRPCa。 我们的研究表明，CTC的纳米力学表型可作为mCRPC的新型有效生物标志物。