OCT4-positive circulating tumor cells may predict a poor prognosis in patients with metastatic castration-resistant prostate cancer treated with abiraterone plus prednisone therapy

Abstract

Octamer-binding transcription factor 4 (OCT4) and circulating tumor cells (CTCs) are key factors associated with tumor metastasis and drug resistance in cancer. The present prospective study aimed to investigate the prevalence of OCT4-positive (OCT4+) CTCs and the potential association with the clinical features and survival of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone + prednisone. In total, 70 patients with mCRPC treated with abiraterone + prednisone were enrolled in the present study and peripheral blood samples were collected prior to treatment initiation to determine CTC count via a Canpatrol system. RNA in situ hybridization was performed for OCT4+ CTC quantification. Lactate dehydrogenase (LDH) was detected by automatic biochemical analyzer (AU54000, OLYMPUS). Results demonstrated that 34 (48.6%), 21 (30.0%) and 15 (21.4%) patients harbored OCT4+ (CTC+/OCT4+) or OCT4-negative CTCs (CTC+/OCT4-) or were CTC-negative (CTC-), respectively. Notably, CTC+/OCT4+ occurrence was associated with visceral metastasis and high levels of LDH. In addition, radiographic progression-free survival [rPFS; median, 15.0, 95% confidence interval (CI), 9.6-20.4 vs. not reached vs. median, 29.5, 95% CI, 18.6-40.4 months; P=0.001] and overall survival (OS) were significantly decreased (median, 27.3, 95% CI, 20.1-34.5 vs. not reached vs. not reached; P=0.016) in CTC+/OCT4+ compared with CTC+/OCT4- and CTC- patients. Subsequently, the adjustment was performed by multivariate Cox regression models, which revealed that CTC+/OCT4+ (vs. CTC+/OCT4- or CTC-) was independently associated with decreased rPFS [hazard ratio (HR), 3.833; P<0.001] and OS (HR, 3.938; P=0.008). In conclusion, OCT4+ CTCs were highly prevalent in patients with mCRPC and associated with visceral metastasis and increased levels of LDH. Thus, the presence of OCT4+ CTCs may serve as an independent prognostic factor for patients with mCRPC treated with abiraterone + prednisone.