Abstract
Awareness of breast cancer has been increasing due to early detection, but the advanced disease has limited treatment options. There has been growing evidence on the role of miRNAs involved in regulating the resistance in several cancers. We performed a comprehensive systematic review and meta-analysis on the role of miRNAs in influencing the chemoresistance and sensitivity of breast cancer. A bibliographic search was performed in PubMed and Science Direct based on the search strategy, and studies published until December 2018 were retrieved. The eligible studies were included based on the selection criteria, and a detailed systematic review and meta-analysis were performed based on PRISMA guidelines. A random-effects model was utilised to evaluate the combined effect size of the obtained hazard ratio and 95% confidence intervals from the eligible studies. Publication bias was assessed with Cochran’s Q test, I2 statistic, Orwin and Classic fail-safe N test, Begg and Mazumdar rank correlation test, Duval and Tweedie trim and fill calculation and the Egger’s bias indicator. A total of 4584 potential studies were screened. Of these, 85 articles were eligible for our systematic review and meta-analysis. In the 85 studies, 188 different miRNAs were studied, of which 96 were upregulated, 87 were downregulated and 5 were not involved in regulation. Overall, 24 drugs were used for treatment, with doxorubicin being prominently reported in 15 studies followed by Paclitaxel in 11 studies, and 5 drugs were used in combinations. We found only two significant HR values from the studies (miR-125b and miR-4443) and our meta-analysis results yielded a combined HR value of 0.748 with a 95% confidence interval of 0.508–1.100; p-value of 0.140. In conclusion, our results suggest there are different miRNAs involved in the regulation of chemoresistance through diverse drug genetic targets. These biomarkers play a crucial role in guiding the effective diagnostic and prognostic efficiency of breast cancer. The screening of miRNAs as a theragnostic biomarker must be brought into regular practice for all diseases. We anticipate that our study serves as a reference in framing future studies and clinical trials for utilising miRNAs and their respective drug targets.
Highlights
Breast cancer is the most prevalent type of cancer in women worldwide [1]
This systematic meta-analysis of “the miRNAs that influence the chemoresistance or chemosensitivity. This systematic meta-analysis of “the miRNAs that influence the chemoresistance or to drugs in breast reviewed over 400 research articles througharticles a systematic
Carefully reviewed over 400 research through a search query from which research articles were scrutinized based on the inclusion criteria
Summary
Breast cancer is the most prevalent type of cancer in women worldwide [1]. This makes it a cause of increasing concern, and it is important to address this issue. It was estimated that 41,070 breast cancer deaths occurred in women during 2017 in the USA alone, making it the second-leading cause of cancer-related death in women [1]. Regardless of this, in developed countries breast cancer is second to lung cancer for cancer-related deaths in women [2]. 25% of female cancer cases in the country are breast cancer [4,5]. The rate of incidence was found to be 25.8 in 100,000 women, and the mortality rate was
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