Association of Circulating Tumor Cells with Inflammatory and Biomarkers in the Blood of Patients with Metastatic Castration-Resistant Prostate Cancer.

Joanna Bialek,Carlotta Lindner,Gerit Theil,Paolo Fornara

doi:10.3390/life11070664

Joanna Bialek, Carlotta Lindner + Show 2 more

Open Access

https://doi.org/10.3390/life11070664

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Abstract

The identification of specific biomarkers that recognize the functional drivers of heterogeneity in prostate cancer (PCa) and personalized treatment remain challenging in systemic medicine. Liquid biopsy allows for the detection and analysis of personalized predictive biomarkers in single blood samples and specifies the current stage of cancer. The aim of our preliminary study was to investigate the association between an elevated circulating tumor cell (CTC) count and the levels of inflammatory factors (IL-6 and IL-8) and biomarkers (DKK-1, PSA, sHER2, and CD44) in patients with metastasized castration-resistant PCa (mCPRC) under chemotherapy and those with localized PCa. Such an association could be used as a component of cancer progression monitoring. We compared the sensitivity and specificity of two CTC isolation platforms. Twenty-eight patients (12 mCRPC and 16 localized PCa patients) were enrolled. Over the study period, the CTC detection rates were 84% with CellCollector® and 73.5% with CellSearch® System in mCPRC patients. The CTC counts determined by the CellSearch® System (CTC_CS) were correlated significantly with the DKK-1, sHER-2, and PSA concentrations in mCRPC patients. The CTC counts captured by CellCollector® demonstrated no significant association with the concentrations of the tested blood-based biomarkers. The CTC_CS count (AUC = 0.9 (95% CI: 0.72–1.0)) and the PSA level (AUC = 0.95 (95% CI: 0.83–1.0)) presented approximately the same sensitivity and specificity for the overall survival of mCRPC patients. For better personalized characterization, further research on CTC phenotyping and their interactions with tumor-associated blood-released factors is needed.

Highlights

Prostate cancer (PCa) is the fifth leading cause of cancer-related death worldwide [1].The incidence increases with each decade of age, and 59% of men over 79 years of age have PCa [2]
The counts determined by the CellSearch® System (CTC_CS) count (AUC = 0.9) and the prostate-specific antigen (PSA) level (AUC = 0.95)
We analyzed the association between inflammatory markers and different biomarkers under therapy in a cohort of patients with PCa-l and mCRPC

Summary

Introduction

The incidence increases with each decade of age, and 59% of men over 79 years of age have PCa [2]. In men aged 75 years and older, the incidence of regional- and distant-stage disease increased from 2013 to 2016 [3]. For 28% of patients with distant metastasis, the estimated survival rate is approximately 5 years [4]. The majority of these patients have multifocal metastatic sites, such as bone and lymph nodes ( vertebrae and pelvis) [5]. Metastatic progression requires certain characteristics of cancer cells, such as plasticity, motility, and colonization, as well as systemic physiological conditions, such as inflammation, which are drivers of metastasis and therapeutic resistance in PCa [6]. Innovations in treatments and combination therapeutic strategies have been developed and have contributed to the therapeutic armamentarium, improving the outcomes from metastatic PCa [8,9]

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