Diagnostic potential of deregulated circulating miRNAs for benign and malignant breast tumors (cohort B).

<p>In ROC curve analysis individual circulating miRNAs were found to have discriminatory accuracy of 0.59–0.75. A panel of seven circulating miRNAs (miR-127-3p, miR-148b, miR-376a, miR-376c, miR-409-3p, miR-652 and miR-801) discriminated between healthy women and those with benign and malignant breast tumors with an AUC of 0.81 and the discriminatory power was superior in younger women (AUC = 0.86).</p

MiRNA levels in benign and malignant breast tissue.

<p>Levels of miR-127-3p, miR-376a and miR-652 are decreased in malignant primary breast cancer when compared to benign breast tissue. Box and whisker plots show RNU6B normalized relative miRNA levels for miR-127-3p and miR-652. As an exception un-normalized Ct values are presented for miR-376a as the normalization strategy was not applicable for this particular miRNA (due to the rather low miR-376a levels in the investigated tissue samples). A two-tailed P<0.05 was considered significant (Wilcoxon rank sum test).</p

Investigation of three new miRNA marker candidates (miR-127-3p, miR-376a and miR-652) in cohort A.

<p>Circulating miR-127-3p, miR-376a and miR-652 are present at elevated levels in the plasma of breast cancer patients when compared to healthy women. A two-tailed P<0.05 was considered significant (Wilcoxon rank sum test).</p

Clinico-pathological characteristics of the malignant breast cancer patients in validation cohorts A and B.

<p>ER = estrogen receptor; PR = progesterone receptor; HER2 =  human epidermal growth factor receptor 2; IDC = invasive ductal carcinoma; ILC = inv. lobular carcinoma.</p>*<p>immunoreactive score (IRS): 0–2 =  ER/PR negative; 3–12 =  ER/PR positive.</p>**<p>IHC-score: 0–1 =  HER2 negative; 2 =  positive if HER2 amplified in FISH/CISH; 3 =  HER2 positive.</p

Independent validation of seven circulating miRNAs (cohort B).

<p>Circulating miR-127-3p, miR-148b, miR-376a, miR-376c, miR-409-3p, miR-652 and miR-801 levels were independently validated as being elevated in the plasma of malignant breast cancer patients compared to healthy women. Circulating miR-148b, miR-652 and miR-801 were also elevated in the plasma of women with benign breast tumors when compared to healthy individuals. A two-tailed P<0.05 was considered significant (Wilcoxon rank sum test).</p