Work

Identification of candidate inverse miRNA–mRNA pairs and an internally validated tissue-based diagnostic model for benign and malignant breast lesions

Year: 2026

Type: article

Abstract: Background: Differentiating malignant breast tumors from benign breast lesions remains clinically important when imaging or pathology is indeterminate. We evaluated candidate inverse miRNA-mRNA expression pairs as a tissue-based adjunctive molecular approach intended to complement, not replace, histopathological diagnosis, with particular relevance to diagnostically challenging lesions such as BI-RADS four or radiologic-pathologic discordant cases. Methods: Public microRNA (miRNA) and messenger RNA (mRNA) datasets were used for candidate discovery and prioritization. An independent reverse-transcription quantitative polymerase chain reaction (RT-qPCR) tissue cohort included 150 breast-lesion samples (68 benign and 82 malignant). Ten candidate axes were measured. A least absolute shrinkage and selection operator (LASSO) logistic-regression model was developed in the training cohort and tested without marker reselection, coefficient refitting, or threshold re-optimization in the internal-validation cohort. Public datasets were used primarily for tumor-versus-normal discovery, whereas benign-versus-malignant evaluation was performed in the independent tissue cohort. Results: miR-205-5p/HMGB3 and miR-96-5p/FOXO1 showed the strongest inverse-expression candidate evidence. The final model retained miR-205-5p, HMGB3, miR-96-5p, FOXO1, and miR-21-5p. In internal validation, the area under the receiver operating characteristic curve (AUC) was 0.894 (95% confidence interval 0.788-0.975), with accuracy 0.844, sensitivity 0.840, and specificity 0.850. Conclusion: A five-marker tissue model discriminated benign from malignant breast lesions in internal validation. miR-205-5p/HMGB3 and miR-96-5p/FOXO1 were the leading inverse-expression candidates. External validation and functional confirmation are required before clinical use.

Source: Frontiers in Molecular Biosciences

DOI: 10.3389/fmolb.2026.1952773

Authors: Xiaoyan Zhao, Hui Feng, Xingxing Wu, Dan Zhao

Institutions: Shanxi Provincial Children's Hospital, Taiyuan Maternity and Child Care Hospital

Language: English

Topic: MicroRNA in disease regulation

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801