TY - JOUR
TI - Prognostic significance of gene expression and DNA methylation markers in circulating tumor cells and paired plasma derived exosomes in metastatic castration resistant prostate cancer
AU - Zavridou, M.
AU - Strati, A.
AU - Bournakis, E.
AU - Smilkou, S.
AU - Tserpeli, V.
AU - Lianidou, E.
JO - Blood cancer journal
PY - 2021
VL - 13
TODO - 4
SP - 1-14
PB - MDPI AG
SN - null
TODO - 10.3390/cancers13040780
TODO - cytokeratin 18;  cytokeratin 19;  cytokeratin 8;  epithelial cell adhesion molecule;  glutathione transferase P1;  messenger RNA;  programmed death 1 ligand 1;  Ras association domain family protein 1A;  Twist related protein 1, adult;  AR 567 gene;  AR FL gene;  AR V7 gene;  Article;  cancer prognosis;  castration resistant prostate cancer;  circulating tumor cell;  CK 18 gene;  CK 19 gene;  CK 8 gene;  controlled study;  DNA methylation;  exosome;  gene;  gene expression;  GSTP1 gene;  human;  human cell;  liquid biopsy;  major clinical study;  male;  metastatic castration resistant prostate cancer;  overall survival;  PD L1 gene;  plasma;  PSMA gene;  RASSF1A gene;  real time polymerase chain reaction;  risk factor;  SCHLAFEN gene;  TWIST1 gene
TODO - Liquid biopsy, based on the analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), provides non‐invasive real‐time monitoring of tumor evolution and therapeutic efficacy. We performed for the first time a direct comparison study on gene expression and DNA methylation markers in CTCs and paired plasma‐derived exosomes and evaluated their prognostic significance in metastatic castration resistant prostate cancer. This prospective liquid biopsy (LB) study was based on a group of 62 metastatic castration resistant prostate cancer (mCRPC) patients and 10 healthy donors (HD) as controls. Identical blood draws were used to: a) enumerate CTC and tumor‐derived extracellular vesicles (tdEVs) using CellSearch (CS) and b) analyze CTCs and paired plasma‐derived exosomes at the gene expression and DNA methylation level. CTCs were enumerated using CellSearch in 57/62 patients, with values ranging from 5 to 854 cells/7.5mLPB. Our results revealed for the first time a significantly higher positivity of gene expression markers (CK‐8, CK‐18, TWIST1, PSMA, AR‐FL, AR‐V7, AR‐567 and PD‐L1 mRNA) in EpCAMpositive CTCs compared to plasma‐derived exosomes. GSTP1, RASSF1A and SCHLAFEN were methylated both in CTC and exosomes. In CTCs, Kaplan–Meier analysis revealed that CK‐19(p = 0.009), PSMA(p = 0.001), TWIST1(p = 0.001) expression and GSTP1(p = 0.001) methylation were correlated with OS, while in exosomes GSTP1 (p = 0.007) and RASSF1A (p = 0.001) methylation was correlated with OS. Our direct comparison study of CTCs and exosomes at gene expression and DNA methylation level, revealed for the first time a significantly higher positivity in EpCAM‐positive CTCs compared to plasma‐derived exosomes. Future perspective of this study should be the evaluation of clinical utility of molecular biomarkers in CTCs and exosomes on independent multicentric cohorts with mCRPC patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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