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Journal Article
EGFR as a stable marker of prostate cancer dissemination to bones
2020
Overview
Background
Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men. Although 5-year survival in patients with localised disease reaches nearly 100%, metastatic disease still remains incurable. Therefore, there is a need for markers indicating metastatic dissemination.
Methods
EGFR overexpression (EGFR
over
) was tracked in 1039 primary tumours, circulating tumour cells from 39 d’Amico high-risk patients and metastatic samples from 21 castration-resistant PCa cases. EGFR status was compared to clinical parameters and multiple molecular factors were assessed using immunohistochemistry and gene ontology analysis. The functional aspect of EGFR was evaluated by plating PC-3 cells on soft and rigid matrices.
Results
EGFR
over
was found in 14% of primary tumours, where it was associated with shorter metastasis-free survival and was an independent indicator of worse overall survival. EGFR
over
correlated with a pro-migratory and pro-metastatic phenotype of tumour cells as well as rich collagen fibre content. All circulating tumour cells (detected in 13% of cases) were positive for EGFR, independent of their EMT-related phenotype. EGFR
over
was more prevalent in castration-resistant bone metastases (29% of patients) and supported growth of human PCa cells on rigid matrices mimicking bone stiffness.
Conclusions
EGFR
over
is a stable, EMT-independent marker of PCa disseminating to rigid organs, preferentially bones.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Biomedical and Life Sciences
/ Bones
/ Collagen
/ Collagen Type I, alpha 1 Chain
/ Epidermal growth factor receptors
/ Epithelial-Mesenchymal Transition
/ Humans
/ Male
/ Mimicry
/ Neoplastic Cells, Circulating - metabolism
/ Neoplastic Cells, Circulating - pathology
/ Oncology
/ Prostatic Neoplasms - metabolism
/ Prostatic Neoplasms - mortality
/ Prostatic Neoplasms - pathology
/ Prostatic Neoplasms, Castration-Resistant - metabolism
/ Prostatic Neoplasms, Castration-Resistant - mortality
/ Prostatic Neoplasms, Castration-Resistant - pathology
/ Tumors
