Abstract
Simple SummaryBreast cancer diagnosis at the initial stage of the disease considerably improves prognosis and survival rates. This retrospective study aimed to develop and validate a plasma microRNA signature as a non-invasive biomarker for early-stage breast cancer diagnosis. We confirmed in a testing cohort of 54 BC patients and 89 healthy volunteers the value of a signature based on miR-30b and miR-99a levels in plasma samples for stage I breast cancer detection. Furthermore, our results were blindly validated in a second cohort of 74 breast cancer and 74 healthy samples. The proposed microRNA signature presented high value as a fast, cost-effective, and non-invasive biomarker for early-stage breast cancer detection, which will lead to a better prognosis for breast cancer patients.The early diagnosis of breast cancer is essential to improve patients’ survival rate. In this context, microRNAs have been described as potential diagnostic biomarkers for breast cancer. Particularly, circulating microRNAs have a strong value as non-invasive biomarkers. Herein, we assessed the potential of a microRNA signature based on miR-30b-5p and miR-99a-5p levels in plasma as a diagnostic biomarker for breast cancer. This two-microRNA signature was constructed by Principal Component Analysis and its prognostic value was assessed in a discovery cohort and blindly validated in a second cohort from an independent institution. ROC curve analysis and biomarker performance parameter evaluation demonstrated that our proposed signature presents a high value as a non-invasive biomarker for very early detection of breast cancer. In addition, pathway enrichment analysis identified three of the well-known pathways involved in cancer as targets of the two microRNAs.
Highlights
Breast cancer (BC) is the most commonly diagnosed cancer in women and the leading cause of cancer-related death in most countries [1]
We propose a combined signature of miR-30b-5p and miR-99a-5p levels in plasma as a candidate biomarker to diagnose very early-stage BC; very early stage was defined as TNM stage I [27]
MiR-30b-5p and miR-99a-5p expression was determined in plasma samples from BC patients and healthy controls
Summary
Breast cancer (BC) is the most commonly diagnosed cancer in women and the leading cause of cancer-related death in most countries [1]. It has been widely demonstrated that the 5-year relative survival of patients diagnosed at stage I arises 100%. Only about 44% of BC patients are diagnosed at an initial stage of the disease despite the demonstrated advantages of screening programs [2,3]. Mammography is the standard breast screening procedure, but its efficacy for dense breasts and women under 40 years old is rather limited. In this context, other techniques such as ultrasounds, magnetic resonance imaging (MRI), or positron emission tomography (PET) may be used, but are not widely available as they are expensive techniques and can lead to over-diagnosis due to a lack of specificity in some cases [4,5]. It is necessary to develop new specific and efficient screening methods for BC
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