Predictive miRNAs Patterns in Blood of Breast Cancer Patients Demonstrating Resistance Towards Neoadjuvant Chemotherapy

Abstract

Objective

The effect of chemotherapy in patients with breast cancer (BC) is uncertain. This study attempted to analyze serum microRNAs (miRNAs) in NAC resistant and sensitive BC patients and develop a miRNA-based nomogram model. To further help clinicians make treatment decisions for hormone receptor-positive patients.

Methods

A total of 110 BC patients with NAC were recruited and assigned in sensitive and resistant group, and 4 sensitive patients and 3 resistant patients were subjected to high-throughput sequencing. The functions of their target genes were analyzed by GO and KEGG. Five BC-related reported miRNAs were selected for expression pattern measurement by RT-qPCR and multivariate logistic analysis. The nomogram model was developed using R 4.0.1, and its predictive efficacy, consistency and clinical application value in development and validation groups were evaluated using ROC, calibration and decision curves.

Results

There were 44 differentially-expressed miRNAs in resistant BC patients. miR-3646, miR-4741, miR-6730-3p, miR-6831-5p and miR-8485 were candidate for resistance diagnosis in BC. Logistic multiple regression analysis showed that miR-4741 (or = 0.30, 95% CI = 0.08–0.63, P = 0.02) and miR-6831-5p (or = 0.48, 95% CI = 0.24–0.78, P = 0.01) were protective factors of BC resistance. The ROC curves showed a sensitivity of 0.884 and 0.750 for miR-4741 and miR-6831-5P as markers of resistance, suggesting that they can be used as independent risk factors for BC resistance. The other 3 miRNAs can be used as calibration factors to establish the risk prediction model of resistance in BC. In risk model, the prediction accuracy of resistance of BC is about 78%. 5-miRNA signature diagnostic models can help clinicians provide personalized treatment for NAC resistance BC patients to improve patient survival.

Conclusion

MiR-4741 and miR-6831-5p are independent risk factors for breast cancer resistance. This study constructed a nomogram model of NAC resistance in BC based on 5 differentially-expressed serum miRNAs.

Keywords:

• breast cancer
• neoadjuvant chemotherapy
• drug resistance
• serum microRNAs
• nomogram model
• 5-miRNAs
• GO and KEGG enrichment analyses

Data Sharing Statement

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

Ethics Statement

This study was a retrospective cohort study approved by the Ethics Committee of Cancer Hospital Affiliated to Xinjiang Medical University, approval number XJZ-CR-2019-017. All participants of this study signed the informed consent before enrollment.

Consent for Publication

Informed consent was obtained from all individual participants included in the study.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was supported by Clinical Research Project by the Affiliated Cancer Hospital of Xinjiang Medical University, project number: 2019CL01001 and Key Laboratory Open Subject of Xinjiang Uyghur Autonomous Region, project number: 2020D04026.