Diagnostic and prognostic value of miR-200 family in breast cancer: A meta-analysis and systematic review

1

Introduction

Breast cancer is reported to be the second most common cancer in women all over the world, accounting for 1 in 4 cancer cases and leading to 15% total of cancer deaths [1] . Based on the expression of estrogen and progesterone receptors (HR), and epidermal growth factor receptor 2 (HER 2), there are four molecular subtype of BC: HR+/HER2− (Luminal A), triple-negative (TNBC), HR+/HER2+ (Luminal B) and HR−/HER2+ (HER2+) subtypes. Luminal A is the most common subtype while HER2+ was the least commonly committed BC type [2] . TNBC is the most aggressive subtype, with an enrichment of stem-like tumor cells [3] . Survival rates are very high when breast cancer is detected early, and an efficient prognostic strategy is available [4] . Thus, discovering methods for early diagnosis and prediction of prognosis are the keys to the survival of patients with breast cancer. Micro RNA (MiRs) has been increasingly seen as potential targets for diagnosis and prognosis of breast cancer [5] .

MicroRNAs are a class of small single-stranded noncoding RNA with significant regulatory roles in gene expressions. They have shown promise for assisting clinical management of breast cancer as diagnostics, prognostic, or predictive biomarkers [6] . The miR-200 family members (miR-200 s) have shown to be involved in the regulation of many critical biological processes such as Epithelial-to-mesenchymal transition (EMT), reverse mesenchymal to epithelial transition (MET), cancer stem cell regulation, cell proliferation and drug resistance [7] . The miR-200 family consists of five members, which are grouped in two independent transcriptional clusters: miR-200a, 200b and 429, located on chromosome 1p36; and miR-200c and 141, located on 12p13 [8] . All miR-200 family members contain a similar seed sequence with only one base difference between the two functional groups. MiR-200c, miR-200b and miR-429 (miR-200 BCE/429) share the same seed sequence AAUACUG, whereas miR-200a and miR-141 (miR-200a/141) contain AACACUG) [9] .

The miR-200 s expression has demonstrated to be deregulated in breast cancer. Numerous researches have been confirmed and some studies have achieved promising results in application of miR-200 family in the BC prognosis 10111213141516171819 . However, the results were inconsistent. For instance, Madhavan et al. [16] reported impact of miR-200 family on predicting PFS and OS in plasma of BC patients. But result of Fontana [14] showed that miR-200 family members were not significant association with BC patients’ outcome. Several studies have also revealed subtype-specific miRNA signatures involved in survival outcomes. Several studies have also revealed the multi-faceted deregulation of miR-200 family in different BC’s subtypes [14] . Indeed, an altered expression profile of miRNAs can distinguish not only between cancer and healthy samples, but they can classify specific molecular subtypes of breast cancer including HER2, Luminal A, Luminal B, and TNBC [14] . The overall validity and accuracy of miR-200 family in BC diagnosis is necessary because of substantial difference in the sensitivity and specificity among different studies [11172021222324 . This meta-analysis is aimed at clarifying the diagnostic and prognostic value of miR-200 family in breast cancer.