Abstract
Success in curing breast cancer largely depends on the stage at diagnosis. Circulating microRNAs are becoming a promising noninvasive biomarker. We postulate that a postoperative decline in circulating microRNAs might have diagnostic and prognostic value. Applying high-throughput microarrays, we screened the dysregulated microRNAs in paired serum samples before and after surgery. The relative concentrations of putative markers between the early breast cancer and cancer-free groups were evaluated in the training set and verified in the validation set. Sensitivity, specificity, and receiver operating characteristic (ROC) curves were used to assess diagnostic value. Survival analysis was performed using Kaplan–Meier estimates and a Cox proportional hazards model. Five microRNAs significantly reduced after surgery were selected for the training set. We found that miR-130b-5p, miR-151a-5p, miR-206, and miR-222-3p were significantly higher in the breast cancer group. Each of the four microRNAs had potential diagnostic value. The combined four microRNAs (training set: area under the curve (AUC) 0.8457; validation set: AUC 0.9309) had better diagnostic value than each single microRNA. MiR-222-3p was an independent prognostic factor for disease-free survival (HR = 13.19; 95% CI, 1.06–163.59; P = 0.045). Patients with no fewer than three highly expressed miRNAs had shorter DFS than patients with 0–2 highly expressed miRNAs (HR = 2.293; 95% CI, 1.128–0.662; P = 0.022). Our findings indicate that postoperatively downregulated circulating miR-130b-5p, miR-151a-5p, miR-206, and miR-222-3p may be potential biomarkers for breast cancer diagnosis and prognosis.
Highlights
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among females, accounting for 30% of all new cancer diagnoses and 21.2% of cancer deaths[1]
Certain serum tumor markers associated with breast cancer, such as carbohydrate antigen 153 (CA153) and carcinoembryonic antigen (CEA), only apply to the monitoring of disease recurrence and not to the Official journal of the Cell Death Differentiation Association
We found that five circulating miRNAs were selected for subsequent testing
Summary
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death among females, accounting for 30% of all new cancer diagnoses and 21.2% of cancer deaths[1]. Death rates have been declining in recent years, largely as a result of early diagnosis and improved treatment[2,3]. The 5-year survival rate of patients with early breast cancer is more than 90%, which is much higher than 20% for those with a primary. Mammography is a widely used tool for breast cancer screening. Its application has become increasingly controversial due to its limitations of underdiagnosis of cancer patients with dense breasts and over-diagnosis of those who might not require surgery[5,6]. Certain serum tumor markers associated with breast cancer, such as carbohydrate antigen 153 (CA153) and carcinoembryonic antigen (CEA), only apply to the monitoring of disease recurrence and not to the Official journal of the Cell Death Differentiation Association
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