TY - JOUR
T1 - Multigene methylation analysis of enriched circulating tumor cells associates with poor progression-free survival in metastatic breast cancer patients
AU - Benezeder, Theresa
AU - Tiran, Verena
AU - Treitler, Alexandra A.N.
AU - Suppan, Christoph
AU - Rossmann, Christopher
AU - Stoeger, Herbert
AU - Cote, Richard J.
AU - Datar, Ram H.
AU - Balic, Marija
AU - Dandachi, Nadia
N1 - Funding Information:
This research was supported by funds of the Oesterreichische Nationalbank, Anniversary Fund, project number 15358 (ND).
Publisher Copyright:
© Benezeder et al.
PY - 2017
Y1 - 2017
N2 - Blood-based biomarkers such as circulating tumor cells (CTCs) provide dynamic real-time assessment of molecular tumor characteristics beyond the primary tumor. The aim of this study was to evaluate the feasibility of a size-based microfilter to assess multigene methylation analysis of enriched CTCs in a prospective proof-of principle study. We examined the quantitative methylation status of nine genes (AKR1B1, BMP6, CST6, HOXB4, HIST1H3C, ITIH5, NEUROD1, RASSF1, SOX17) in enriched CTCs from metastatic breast cancer patients. Feasibility and clinical performance testing were assessed in a test set consisting of 37 patients and 25 healthy controls. With established cut-off values from the healthy control group, methylation of enriched CTCs was detected in at least one gene in 18/37 patients (48.6%), while 97.8% of all control samples were unmethylated. Patients with CTCs unmethylated for CST6, ITIH5, or RASSF1 showed significantly longer PFS compared to patients with corresponding enriched methylated CTCs. This proof-of-principle study shows the feasibility of a size-based microfilter to enrich and analyze multigene methylation profile of CTCs from metastatic breast cancer patients. For the first time, we report that multigene methylation analysis of enriched CTCs provides prognostic information in metastatic breast cancer patients.
AB - Blood-based biomarkers such as circulating tumor cells (CTCs) provide dynamic real-time assessment of molecular tumor characteristics beyond the primary tumor. The aim of this study was to evaluate the feasibility of a size-based microfilter to assess multigene methylation analysis of enriched CTCs in a prospective proof-of principle study. We examined the quantitative methylation status of nine genes (AKR1B1, BMP6, CST6, HOXB4, HIST1H3C, ITIH5, NEUROD1, RASSF1, SOX17) in enriched CTCs from metastatic breast cancer patients. Feasibility and clinical performance testing were assessed in a test set consisting of 37 patients and 25 healthy controls. With established cut-off values from the healthy control group, methylation of enriched CTCs was detected in at least one gene in 18/37 patients (48.6%), while 97.8% of all control samples were unmethylated. Patients with CTCs unmethylated for CST6, ITIH5, or RASSF1 showed significantly longer PFS compared to patients with corresponding enriched methylated CTCs. This proof-of-principle study shows the feasibility of a size-based microfilter to enrich and analyze multigene methylation profile of CTCs from metastatic breast cancer patients. For the first time, we report that multigene methylation analysis of enriched CTCs provides prognostic information in metastatic breast cancer patients.
KW - Circulating tumor cells
KW - Enrichment
KW - Metastatic breast cancer
KW - Methylation
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=85032702200&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.21426
DO - 10.18632/oncotarget.21426
M3 - Article
C2 - 29190932
AN - SCOPUS:85032702200
SN - 1949-2553
VL - 8
SP - 92483
EP - 92496
JO - Oncotarget
JF - Oncotarget
IS - 54
ER -