Graphene Oxide-Based Highly Sensitive Assay of Circulating MicroRNAs for Early Prediction of the Response to Neoadjuvant Chemotherapy in Breast Cancer

Abstract

The response to neoadjuvant chemotherapy (NAC) is highly correlated with survival in breast cancer (BC) patients. The early prediction of the response to NAC could facilitate treatment adjustments on a patient-by-patient basis, which would improve patient outcomes and survival. Conventional techniques used for detecting circulating microRNAs (miRNAs), which act as biomarkers for the early prediction of NAC efficacy in BC patients, are associated with limitations such as low sensitivity and specificity. We designed a highly sensitive graphene oxide (GO)based qRT-PCR method for detecting miRNAs associated with the chemotherapeutic response in BC patients. The results showed that miRNA levels at both the baseline and end of the first NAC cycle could help distinguish NAC responders from NAC nonresponders; BC patients with lower plasma miRNA levels were more likely to achieve pathological complete remission. Thus, GO-based qRT-PCR could facilitate early prediction of NAC efficacy in BC patients.

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

“…Overall, nine studies (60%) [ 26 , 28 , 55 , 56 , 58 , 59 , 60 , 62 , 63 ] received a “low ROB”, four studies (27%) [ 57 , 61 , 65 , 66 ] were assigned an “unclear ROB” rating, and two studies (13%) [ 54 , 64 ] were assigned a “high ROB”. The omission of appropriate statistical analysis for predicting model validation and information in the first three domains (i.e., participants, predictors, and outcome) was a frequent source of bias in terms of high and unclear judgment.…”

“…We did not assess publication bias with funnel plot analysis since our meta-analysis included a maximum of nine studies, and the inclusion of fewer than ten studies may not provide enough power to test the real asymmetry [ 68 ]. Stevic 2018 [ 56 ], McGuire 2020 [ 54 ], Li 2022 [ 65 ].…”

“…Despite the methodological limitations of a comprehensive quantitative analysis involving multiple miRNAs, our findings from both models support the promising role of selected circulating miRNAs, namely, miR-21-5p and miR-155-5p, in predicting responses to NAC in a mixed population of BC patients. Specifically, lower levels of circulating miR-21-5p and miR-155-5p (evaluated at baseline and as a change from a timepoint during or after NAC compared to the baseline) were observed among BC patients with pCR compared to those with residual disease in the studies included the meta-analysis [ 26 , 28 , 54 , 56 , 59 , 61 , 65 ]. Thus, a low level of these two circulating miRNAs could help to identify patients who will benefit from NAC.…”

Circulating microRNAs in Cancer: A 5-Year Update with a Focus on Breast and Lung Cancers

“…Moreover, the authors used this method to assess the expression levels of three circulating miRNAs, such as miR-21, miR-155, and miR-195, in a BC cohort treated with NAC. They showed that miRNA levels seemed to distinguish the NAC-responder patients from those non-responders [ 49 ]. Another method carried out to improve the standard qRT-PCR technique for miRNA quantitative analysis is the branched rolling circle amplification (BRCA).…”

Potential Impact of Preoperative Circulating Biomarkers on Individual Escalating/de-Escalating Strategies in Early Breast Cancer

“…However, low sensitivity and low specificity of detection techniques limit miRNA analysis, and new methods are under development. Li and colleagues, for instance, devised a new graphene oxide (GO)-based qRT-PCR method for detecting miRNAs and distinguishing NACT responders in eBC patients [186]. Further results are needed to better understand how miRNA may become useful for patient stratification and for defining personalized treatment in eBC.…”