Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis

TY - JOUR

T1 - Circulating miRNAs with prognostic value in metastatic breast cancer and for early detection of metastasis

AU - Madhavan, Dharanija

AU - Peng, Cike

AU - Wallwiener, Markus

AU - Zucknick, Manuela

AU - Nees, Juliane

AU - Schott, Sarah

AU - Rudolph, Anja

AU - Riethdorf, Sabine

AU - Trumpp, Andreas

AU - Pantel, Klaus

AU - Sohn, Christof

AU - Chang-Claude, Jenny

AU - Schneeweiss, Andreas

AU - Burwinkel, Barbara

N1 - © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2016

Y1 - 2016

N2 - Metastasis is the principal cause of high morbidity and mortality among breast cancer (BC) patients. Identification of markers that can be routinely monitored to predict onset of metastasis in BC patients and prognosis of metastatic breast cancer (MBC) patients would increase their median survival. In the present study, plasma miRNAs of 40 MBC patients were profiled by TaqMan low density arrays and miRNAs with prognostic capacity were identified. The candidates were validated initially in the samples of 237 MBC patients and subsequently in 335 samples from an independent study cohort of BC patients. Sixteen miRNAs were established to be significantly associated with overall survival, and were termed as prognostic miRNA panel template (PROMPT). These included miR-141, miR-144, miR-193b, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-215, miR-365, miR-375, miR-429, miR-486-5p, miR-801, miR-1260, and miR-1274a. Additionally, eleven of these miRNAs were also associated with progression-free survival. Their prognostic significance was further confirmed in samples from a second study cohort of BC patients. In addition, miR-200a, miR-200b, miR-200c, miR-210, miR-215, and miR-486-5p were found to be significantly associated with onset of metastasis up to 2 years prior to clinical diagnosis in BC patients. We have thus identified panels of miRNAs, which include metastasis promoting miR-200 family and miR-203, as well as oncogenic and tumor suppressive miRNAs, that can serve as prognostic markers for MBC, and early detection markers of metastasis in BC.

AB - Metastasis is the principal cause of high morbidity and mortality among breast cancer (BC) patients. Identification of markers that can be routinely monitored to predict onset of metastasis in BC patients and prognosis of metastatic breast cancer (MBC) patients would increase their median survival. In the present study, plasma miRNAs of 40 MBC patients were profiled by TaqMan low density arrays and miRNAs with prognostic capacity were identified. The candidates were validated initially in the samples of 237 MBC patients and subsequently in 335 samples from an independent study cohort of BC patients. Sixteen miRNAs were established to be significantly associated with overall survival, and were termed as prognostic miRNA panel template (PROMPT). These included miR-141, miR-144, miR-193b, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-215, miR-365, miR-375, miR-429, miR-486-5p, miR-801, miR-1260, and miR-1274a. Additionally, eleven of these miRNAs were also associated with progression-free survival. Their prognostic significance was further confirmed in samples from a second study cohort of BC patients. In addition, miR-200a, miR-200b, miR-200c, miR-210, miR-215, and miR-486-5p were found to be significantly associated with onset of metastasis up to 2 years prior to clinical diagnosis in BC patients. We have thus identified panels of miRNAs, which include metastasis promoting miR-200 family and miR-203, as well as oncogenic and tumor suppressive miRNAs, that can serve as prognostic markers for MBC, and early detection markers of metastasis in BC.

U2 - 10.1093/carcin/bgw008

DO - 10.1093/carcin/bgw008

M3 - SCORING: Journal article

C2 - 26785733

VL - 37

SP - 461

EP - 470

JO - CARCINOGENESIS

JF - CARCINOGENESIS

SN - 0143-3334

IS - 5

ER -