Impact of circulating miRNA-373 on breast cancer diagnosis through targeting VEGF and cyclin D1 genes

Abstract

Background: Breast cancer (BC) is the common primary tumor among females. Hence, there is an urgent need to improve the early prediction and diagnosis of BC. For that reason, the object of the current study is to analyze the expression levels of miRNA-373 and its target genes including vascular endothelial growth factor (VEGF) and cyclin D1 in women with BC.

Results: Upregulation of miRNA-373 and its target genes was observed in BC patients followed by patients with benign breast lesions compared to downregulation in controls. There was a significant association between the expression level of miRNA-373 and all clinical features. The same associations were observed between its target genes and all clinico-pathological features except hormonal status. The correlation between miRNA-373 and both genes was significant.

Conclusions: Our results prove that miRNA-373, as an oncomir, would be a vital biomarker for BC diagnosis and prognosis by targeting both VEGF and cyclin D1.

Keywords: Breast cancer; Clinico-pathological characteristics; Cyclin D1; Diagnosis; MicroRNA; VEGF.

Fig. 1

Receiver operating characteristic curve for investigated markers. Arrows donate to the cut value for investigated markers: for VEGF, the cutoff was 38 ng/ml with sensitivity at 92.35% and specificity at 96.8% at standard error 0.0077 and CI% 0.955–0.991, area under the curve 0.978; for cyclin D1, the cutoff was 38 ng/ml with sensitivity at 91.8% and specificity at 96% at standard error 0.008 and CI% 0.952–0.989, area under the curve 0.975; and for miR-373, the cutoff was 360 ng/ml with sensitivity at 90.8% and specificity at 98.4% at standard error 0.007 and CI% 0.958–0.992, area under the curve 0.98

Fig. 2

Relation between miR-373 and clinico-pathological features. a Pathological types (DCI vs IDC) at X²=3.5 (P<0.001). b Clinical stages (stage I to IV) at X²=10 (P=0.012). c Histological grading (grade I to III) at X²=10 (P=0.006). d Lymph node involvement (negative involvement vs positive involvement) (X²=4.43, P<0.001). X² resembles the chi-square test between investigated variables

Fig. 3

Relation between VEGF and clinico-pathological features. a Pathological types (DCI vs IDC) at Z=2.8 (P=0.004). b Clinical stages (stage I to IV) at X²=10 (P=0.018). c Histological grading (grade I to III) at X²=6.4 (P=0.04). d Lymph node involvement (negative involvement vs positive involvement) (Z=3.6, P=0.003). Statistical analysis was done using the non-parametric test; as for two variables, the Mann-Whitney U test (Z-value) was used; and for more than two variables, the Kruskal-Wallis H test (X² test) was used

Fig. 4

Relation between cyclin D1 and clinico-pathological features. a Pathological types (DCI vs IDC) at Z=3 (P=0.003). b Clinical stages (stage I to IV) at X²=9 (P=0.019). c Histological grading (grade I to III) at X²=6.9 (P=0.03). Statistical analysis was done using the non-parametric test; as for two variables, the Mann-Whitney U test (Z-value) was used; and for more than two variables, the Kruskal-Wallis H test (X² test) was used