Abstract
Introduction: Circulating tumor cells (CTCs) are important prognostic indicators for malignancies. However, a reliable positive/negative cutoff value of non-epithelial (NE(+): hybrid and mesenchymal) CTCs phenotype in prostate cancer (PCa) patients has not been established. Here, we aimed to determine the cutoff value and the prognostic value of NE(+) CTCs in high-risk prostate cancer (HRPC) patients after radical prostatectomy (RP). Methods: The cutoff value of NE(+) CTCs was established in spiking experiments, and CTCs were detected in 208 HRPC patients using the CanPatrol(TM) platform. The expression and function of COL1A1 in PCa were examined via qRT-PCR, Western blot, wound healing assay, Transwell assay, and immunohistochemistry (IHC). Results: The cutoff value of NE(+) CTCs was determined to be 45% by spiking experiments. In 208 HRPC patients, the NE(+) CTCs positive group had higher prostate-specific antigen (PSA) levels, more advanced pathological tumor stage, and lymph node stage (P < 0.001, P = 0.002 and 0.002, respectively). Besides, patients with NE(+) CTCs ≥ 45% had a shorter median progression-free survival (PFS) than those with NE(+) CTCs < 45% (44.5 vs. 51.0 months, hazard ratio = 3.31, P < 0.05). Moreover, we identified that COL1A1 was associated with a high proportion of NE(+) CTCs in HRPC patients via an EMT mechanism. Conclusion: Our findings suggest that NE(+) CTCs represent a reliable prognostic indicator for HRPC patients and that targeting COL1A1 may prevent the formation of NE(+) CTCs.