Abstract

BackgroundMicroRNA-34a (miR-34a) is a master regulator of tumor suppression in breast cancer (BC). This systematic review aims to analyze the diagnostic accuracy of miR-34a in the detection of BC as a biomarker.ResultsA total of 1858 BC cases and 494 controls from thirteen eligible studies reported in 9 publications were included. The overall pooled sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were 85.50% (95% CI: 83.80-87.00%), 70.00% (95% CI: 65.80–74.10%), 0.29 (95% CI: 0.19–0.43), 2.58 (95% CI: 1.91–3.43), and 9.39 (95% CI: 5.47–16.12), respectively. Similarly, the overall area under the curve (AUC) of the summary receiver operating characteristic (SROC) was 0.80, indicating the high conservation of miR-34a as a biomarker. Furthermore, subgroup analysis suggested that the use of miR-34a as a biomarker is more accurate in tissue-based sample of invasive BC. We also indicated that miR-34a is a capable biomarker in diagnosing BC in people of Caucasian descent.Materials and MethodsA systematic search was conducted for eligible publications that address miR-34a expression level in BC cases and noncancerous controls. Diagnostic capacity of miR-34a for BC was assessed using pooled sensitivity and specificity, DOR, and AUC of SROC. PLR and NLR were verified to estimate the miR-34a diagnostic accuracy in clinical level. The quality of the included studies was assessed by QUADAS-2.ConclusionsThese findings suggest miR-34a is a promising non-invasive biomarker in diagnosing BC. Well-designed cohort studies should be implemented to warrant the diagnostic value of miR-34a in clinical purposes.

Highlights

  • Breast cancer (BC) is the second leading cause of mortality in females worldwide and the most frequently diagnosed cancer in the USA, estimated 14.6% (1.68 million) of all new cancer cases and 40,290 of all cancer-related deaths in 2015 [1, 2]

  • The overall pooled sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), and diagnostic odds ratio (DOR) were 85.50%, 70.00%, 0.29, 2.58, and 9.39, respectively

  • Subgroup analysis suggested that the use of miR-34a as a biomarker is more accurate in tissue-based sample of invasive breast cancer (BC)

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Summary

Introduction

Breast cancer (BC) is the second leading cause of mortality in females worldwide and the most frequently diagnosed cancer in the USA, estimated 14.6% (1.68 million) of all new cancer cases and 40,290 of all cancer-related deaths in 2015 [1, 2]. Since the BC is a genetically heterogeneous disease, clinical and diagnostic outcomes are widely disparate and routine clinicpathological factors for diagnosis and/or prognosis of BC are potentially limited [3]. Unavailability of hospital insurance, low sensitivity and specificity, high false positives, complexity, and high costs are main limitations of these diagnostic biomarkers to monitor disease progression or recurrence. Protein-based circulating tumor biomarkers, such as www.impactjournals.com/oncotarget carbohydrate antigen 15–3 and tissue polypeptide specific antigen, are already applied in clinical diagnoses, but have low diagnostic sensitivity and specificity [6, 7]. Novel noninvasive diagnostic biomarkers with high sensitivity and specificity for early-stage BC detection are in great need [8]. This systematic review aims to analyze the diagnostic accuracy of miR-34a in the detection of BC as a biomarker

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