Gene expression alterations during development of castration-resistant prostate cancer are detected in circulating tumor cells

• Development of castration-resistant prostate cancer (CRPC) is associated with alterations in gene expression involved in steroidogenesis and androgen signaling. This study investigates whether gene expression changes related to CRPC development can be identified in circulating tumor cells (CTCs). Gene expression in paired CTC samples from 29 patients, before androgen deprivation therapy (ADT) and at CRPC relapse, was compared using a panel including 47 genes related to prostate cancer progression on a qPCR platform. Fourteen genes displayed significantly changed gene expression in CTCs at CRPC relapse compared to before start of ADT. The genes with increased expression at CRPC relapse were related to steroidogenesis, AR-signaling, and anti-apoptosis. In contrast, expression of prostate markers was downregulated at CRPC. We also show that midkine (MDK) expression in CTCs from metastatic hormone-sensitive prostate cancer (mHSPC) was associated to short cancer-specific survival (CSS). In conclusion, this study shows that gene expression patterns in CTCs reflect the development of CRPC, and that MDK expression levels in CTCs are prognostic for cancer-specific survival in mHSPC. This study emphasizes the role of CTCs in exploring mechanisms of therapy resistance, as well as a promising biomarker for prognostic and treatment-predictive purposes in advanced mHSPC. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Urology and Nephrology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Biomarker

CRPC

CTC

Hormone-sensitive prostate cancer

Liquid biopsy

Resistance mechanisms

abiraterone acetate

androgen receptor

bicalutamide

cabazitaxel

cyclophosphamide

docetaxel

enzalutamide

midkine

radium chloride ra 223

aged

AGR2 gene

AKR1C3 gene

androgen deprivation therapy

apoptosis

AR gene

Article

BCL2 gene

cancer prognosis

cancer recurrence

cancer specific survival

carcinogenesis

castration resistant prostate cancer

circulating tumor cell

clinical article

disease association

down regulation

EPCAM gene

epithelial mesenchymal transition

FOLH1 gene

gene

gene expression profiling

gene mutation

HER2 gene

human

human cell

human tissue

KLK3 gene

KRT19 gene

male

molecular phylogeny

PSCA gene

real time polymerase chain reaction

signal transduction

SRD5A1 gene

steroidogenesis

survival rate

survival time

Sweden

TACSTD2 gene

TWIST1 gene

CTC

Publikations- och innehållstyp

ref (ämneskategori)

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