Deregulated serum concentrations of circulating cell-free microRNAs miR-17, miR-34a, miR-155, and miR-373 in human breast cancer development and progression

TY - JOUR

T1 - Deregulated serum concentrations of circulating cell-free microRNAs miR-17, miR-34a, miR-155, and miR-373 in human breast cancer development and progression

AU - Eichelser, Corinna

AU - Flesch-Janys, Dieter

AU - Chang-Claude, Jenny

AU - Pantel, Klaus

AU - Schwarzenbach, Heidi

PY - 2013/10/1

Y1 - 2013/10/1

N2 - BACKGROUND: MicroRNAs (miRs) are small, noncoding RNAs that target genes involved in tumor development and progression. In the current study, we investigated the use of circulating miR concentrations as biomarkers in the serum of breast cancer patients.METHODS: We analyzed serum samples from 120 patients with primary breast cancer after surgery and before chemotherapy (M0, classified into 3 subgroups of 40 patients with progesterone/estrogen-positive, HER2-positive, and triple-negative cancer), 32 patients with overt metastasis (M1), and 40 healthy women. Using quantitative TaqMan MicroRNA PCR, we measured the relative concentrations of 6 circulating microRNAs (miR-10b, -17, -34a, -93, -155, and -373) known to be relevant for tumor development and progression. The data were correlated with clinicopathologic risk factors, with particular reference to HER2 and hormone receptor status of the primary tumor and the presence of metastases.RESULTS: The relative serum concentrations of circulating miR-34a [P = 0.013, area under the curve (AUC) 0.636], miR-93 (P = 0.001, AUC 0.699), and miR-373 (P = 0.0001, AUC 0.879) were significantly different between M0 breast cancer patients and healthy women, whereas miR-17 (P = 0.002, AUC 0.679) and miR-155 (P = 0.0001, AUC 0.781) were differently expressed between M0 and M1 patients. Increased concentrations of miR-373 were associated with negative HER2 status of the primary tumor (P = 0.0001). Deregulated concentrations of miR-17 (P = 0.019) and miR-34a (P = 0.029) were detected in patients with progesterone/estrogen receptor-positive and -negative status, respectively.CONCLUSIONS: Our findings indicate that serum concentrations of deregulated microRNAs may be linked to a particular biology of breast carcinomas favoring progression and metastatic spread.

AB - BACKGROUND: MicroRNAs (miRs) are small, noncoding RNAs that target genes involved in tumor development and progression. In the current study, we investigated the use of circulating miR concentrations as biomarkers in the serum of breast cancer patients.METHODS: We analyzed serum samples from 120 patients with primary breast cancer after surgery and before chemotherapy (M0, classified into 3 subgroups of 40 patients with progesterone/estrogen-positive, HER2-positive, and triple-negative cancer), 32 patients with overt metastasis (M1), and 40 healthy women. Using quantitative TaqMan MicroRNA PCR, we measured the relative concentrations of 6 circulating microRNAs (miR-10b, -17, -34a, -93, -155, and -373) known to be relevant for tumor development and progression. The data were correlated with clinicopathologic risk factors, with particular reference to HER2 and hormone receptor status of the primary tumor and the presence of metastases.RESULTS: The relative serum concentrations of circulating miR-34a [P = 0.013, area under the curve (AUC) 0.636], miR-93 (P = 0.001, AUC 0.699), and miR-373 (P = 0.0001, AUC 0.879) were significantly different between M0 breast cancer patients and healthy women, whereas miR-17 (P = 0.002, AUC 0.679) and miR-155 (P = 0.0001, AUC 0.781) were differently expressed between M0 and M1 patients. Increased concentrations of miR-373 were associated with negative HER2 status of the primary tumor (P = 0.0001). Deregulated concentrations of miR-17 (P = 0.019) and miR-34a (P = 0.029) were detected in patients with progesterone/estrogen receptor-positive and -negative status, respectively.CONCLUSIONS: Our findings indicate that serum concentrations of deregulated microRNAs may be linked to a particular biology of breast carcinomas favoring progression and metastatic spread.

KW - Aged

KW - Breast Neoplasms

KW - Case-Control Studies

KW - Female

KW - Humans

KW - MicroRNAs

KW - Middle Aged

KW - Neoplasm Metastasis

KW - Receptor, erbB-2

KW - Receptors, Estrogen

KW - Receptors, Progesterone

KW - Triple Negative Breast Neoplasms

U2 - 10.1373/clinchem.2013.205161

DO - 10.1373/clinchem.2013.205161

M3 - SCORING: Journal article

C2 - 23748853

VL - 59

SP - 1489

EP - 1496

JO - CLIN CHEM

JF - CLIN CHEM

SN - 0009-9147

IS - 10

ER -