Assessment of Total, PTEN–, and AR-V7+ Circulating Tumor Cell Count by Flow Cytometry in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide

Lorenzo, Giuseppe Di; Zappavigna, Silvia; Crocetto, Felice; Giuliano, Mario; Ribera, Dario; Morra, Rocco; Scafuri, Luca; Verde, Antonio; Bruzzese, Dario; Iaccarino, Simona; Costabile, Ferdinando; Onofrio, Livia; Viggiani, Martina; Palmieri, Alessandro; Placido, Pietro De; Marretta, Antonella Lucia; Pietroluongo, Erica; Luce, Amalia; Abate, Marianna; Navaeiseddighi, Zahrasadat; Caputo, Vincenzo; Celentano, Giuseppe; Longo, Nicola; Ferro, Matteo; Morelli, Franco; Facchini, Gaetano; Caraglia, Michele; Placido, Sabino De; Buonerba, Carlo

doi:10.1016/j.clgc.2021.03.021

Cited by 19 publications

(14 citation statements)

References 30 publications

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“…Normal prostate metabolism is coordinated by androgen receptor signaling and characterized by a physiological truncation of the Krebs cycle to enable the production and secretion of citrate into prostatic fluid [ 26 , 27 , 28 ]. It was reported that androgens, which bind to androgen receptors, influence prostate cancer development.…”

Section: Discussionmentioning

confidence: 99%

Citric Acid as a Potential Prostate Cancer Biomarker Determined in Various Biological Samples

et al. 2022

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Despite numerous studies, the molecular mechanism of prostate cancer development is still unknown. Recent investigations indicated that citric acid and lipids—with a special emphasis on fatty acids, steroids and hormones (ex. prolactin)—play a significant role in prostate cancer development and progression. However, citric acid is assumed to be a potential biomarker of prostate cancer, due to which, the diagnosis at an early stage of the disease could be possible. For this reason, the main goal of this study is to determine the citric acid concentration in three different matrices. To the best of our knowledge, this is the first time for citric acid to be determined in three different matrices (tissue, urine and blood). Samples were collected from patients diagnosed with prostate cancer and from a selected control group (individuals with benign prostatic hyperplasia). The analyses were performed using the rapid fluorometric test. The obtained results were correlated with both the histopathological data (the Gleason scale as well as the Classification of Malignant Tumors (pTNM) staging scale) and the biochemical data (the values of the following factors: prostate specific antigen, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, total cholesterol, creatinine and prolactin) using chemometric methods. For tissue samples, the results indicated a decreased level of citric acid in the case of prostate cancer. The analyte average concentrations in serum and urine appeared to be corresponding and superior in the positive cohort. This trend was statistically significant in the case of urinary citric acid. Moreover, a significant negative correlation was demonstrated between the concentration of citric acid and the tumor stage. A negative correlation between the total cholesterol and high-density lipoprotein and prolactin was particularly prominent in cancer cases. Conversely, a negative association between low-density lipoprotein and prolactin levels was observed solely in the control group. On the basis of the results, one may assume the influence of hormones, particularly prolactin, on the development of prostate cancer. The present research allowed us to verify the possibility of using citric acid as a potential biomarker for prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Citric Acid as a Potential Prostate Cancer Biomarker Determined in Various Biological Samples

et al. 2022

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“…After applying all the selection criteria, the final sample comprised 46 articles on metastatic PC [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ] ( Supplementary Table S1 ) and 15 articles on localized PC [ 55 , 56 , 57 , 58 , 59 , 60 …”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis

Enikeev

Morozov

Babaevskaya

et al. 2022

Cancers

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The purpose of the review is to summarize the recent data on circulating tumor cells (CTC) use in clinical practice. We performed a systematic literature search using two databases (Medline and Scopus) over the past five years and the following terms: (CTC OR “circulating tumor cells” OR “liquid biopsy”) AND prostate. The primary outcome was CTC predictive value for prostate cancer (PC) progression and survival. The secondary outcomes were the CTC predictive value for therapy response and the results of CTC detection depending on the assessment method. In metastatic PC, the CTC count showed itself to be a prognostic marker in terms of clinically important features, namely survival rates and response to treatment. CTC concentration was significantly associated with the overall survival and progression-free survival rates. A strong association between the overall survival or progression-free survival rate and CTC concentration could be observed. Variant-7 androgen receptors-positive (AR-V7-positive) patients showed a poor response to androgen receptor signaling (ARS) inhibitors, but this did not compromise their response to taxanes. In localized PC, only positive Cluster of Differentiantion 82 protein (CD82+) correlated with a higher survival rate. CTC count and AR-V7 expression showed itself to be a valuable biomarker for survival in metastatic PC and response to ARS-inhibitors. CTC diagnostic performance for localized PC or for screening and early detection is not high enough to show additional value over the other biomarkers.

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“…The authors demonstrated that more than two PTEN negative CTCs were associated with a 3.96 hazard ratio for progression or death compared with CRPC patients with less than two PTEN negative CTCs. Moreover, a high CTC AR-V7 positive count (0–20) was associated with a radiographic progression-free survival in ezalutamid-treated patients [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

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

Theil

Lindner

Białek

et al. 2021

Life

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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.

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Assessment of Total, PTEN–, and AR-V7+ Circulating Tumor Cell Count by Flow Cytometry in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide

Cited by 19 publications

References 30 publications

Citric Acid as a Potential Prostate Cancer Biomarker Determined in Various Biological Samples

Citric Acid as a Potential Prostate Cancer Biomarker Determined in Various Biological Samples

A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis

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

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