Prognostic and diagnostic values of non-coding RNAs as biomarkers for breast cancer: An umbrella review and pan-cancer analysis

Abstract

Background: Breast cancer (BC) is the most common cancer in women. The incidence and morbidity of BC are expected to rise rapidly. The stage at which BC is diagnosed has a significant impact on clinical outcomes. When detected early, an overall 5-year survival rate of up to 90% is possible. Although numerous studies have been conducted to assess the prognostic and diagnostic values of non-coding RNAs (ncRNAs) in breast cancer, their overall potential remains unclear. In this field of study, there are various systematic reviews and meta-analysis studies that report volumes of data. In this study, we tried to collect all these systematic reviews and meta-analysis studies in order to re-analyze their data without any restriction to breast cancer or non-coding RNA type, to make it as comprehensive as possible.Methods: Three databases, namely, PubMed, Scopus, and Web of Science (WoS), were searched to find any relevant meta-analysis studies. After thoroughly searching, the screening of titles, abstracts, and full-text and the quality of all included studies were assessed using the AMSTAR tool. All the required data including hazard ratios (HRs), sensitivity (SENS), and specificity (SPEC) were extracted for further analysis, and all analyses were carried out using Stata.Results: In the prognostic part, our initial search of three databases produced 10,548 articles, of which 58 studies were included in the current study. We assessed the correlation of non-coding RNA (ncRNA) expression with different survival outcomes in breast cancer patients: overall survival (OS) (HR = 1.521), disease-free survival (DFS) (HR = 1.33), recurrence-free survival (RFS) (HR = 1.66), progression-free survival (PFS) (HR = 1.71), metastasis-free survival (MFS) (HR = 0.90), and disease-specific survival (DSS) (HR = 0.37). After eliminating low-quality studies, the results did not change significantly. In the diagnostic part, 22 articles and 30 datasets were retrieved from 8,453 articles. The quality of all studies was determined. The bivariate and random-effects models were used to assess the diagnostic value of ncRNAs. The overall area under the curve (AUC) of ncRNAs in differentiated patients is 0.88 (SENS: 80% and SPEC: 82%). There was no difference in the potential of single and combined ncRNAs in differentiated BC patients. However, the overall potential of microRNAs (miRNAs) is higher than that of long non-coding RNAs (lncRNAs). No evidence of publication bias was found in the current study. Nine miRNAs, four lncRNAs, and five gene targets showed significant OS and RFS between normal and cancer patients based on pan-cancer data analysis, demonstrating their potential prognostic value.Conclusion: The present umbrella review showed that ncRNAs, including lncRNAs and miRNAs, can be used as prognostic and diagnostic biomarkers for breast cancer patients, regardless of the sample sources, ethnicity of patients, and subtype of breast cancer.

Unlocking the Potential of Circulating miRNAs in the Breast Cancer Neoadjuvant Setting: A Systematic Review and Meta-Analysis

“…Therefore, further studies incorporating more standardized methodological approaches are warranted to explore the prognostic role of tissue miR-21-5p and miR-155-5p in BC, particularly using TCGA data. Besides TCGA-based studies, different authors have analyzed the association of tissue miR-21-5p and miR-155-5p with BC prognosis [ 105 , 106 , 107 ]. A recent meta-analysis conducted by Bahramy and colleagues demonstrated a significant association between poor overall survival and miR-21-5p expression in BC tissues (HR = 1.93 [95% CI: 1.62–2.30] p = 0.02) [ 105 ].…”

“…Besides TCGA-based studies, different authors have analyzed the association of tissue miR-21-5p and miR-155-5p with BC prognosis [ 105 , 106 , 107 ]. A recent meta-analysis conducted by Bahramy and colleagues demonstrated a significant association between poor overall survival and miR-21-5p expression in BC tissues (HR = 1.93 [95% CI: 1.62–2.30] p = 0.02) [ 105 ]. Similarly, in the updated meta-analysis conducted by Wu et al, miRNA-155-5p was found to be significantly associated with poor overall survival among cancer patients (HR = 1.38 [95% CI: 1.25–1.54] p < 0.001), although this association was not maintained in a BC subgroup analysis [ 106 ].…”

Decoding contextual crosstalk: revealing distinct interactions between non-coding RNAs and unfolded protein response in breast cancer

“…Researchers have shifted their focus to studying alternative biological targets and novel signaling pathways that can effectively inhibit breast cancer growth and metastasis [ 86 ]. Numerous studies have indicated that ncRNAs exhibit different expressions in various stages of development and pathological conditions, including breast cancer [ 87 – 90 ]. This suggests that ncRNAs may serve as an alternative treatment for cancer prevention and management in the future.…”

Design and Fabrication of a Nanobiosensor for the Detection of Cell-Free Circulating miRNAS-LncRNAS-mRNAS Triad Grid

“…Increasing scientific research of ncRNAs has opened up new avenues for investigating the ongoing aberrant mechanisms of different chronic and age-associated diseases and identifying the molecular targets for diagnosis and therapeutics . It is now evident that the aberrant ceRNA network plays a vital role in the onset and progression of several noncommunicable diseases and malignancies, including breast cancer (BC), the primary source of cancer-related complications in women around the world. , As per recent estimates, one in every 20 women worldwide and one in eight women in countries with high incomes are affected by BC. Although the average mortality rate from BC has fallen due to the recent developments in therapeutic procedures, early detection and immediate treatment are two crucial factors for the cure of BC .…”