Two-miRNA serum signature discriminates invasive ductal breast carcinoma in case-control cohorts

A study reported in Molecular Biology Reports identified a two-microRNA serum signature, miR-6838-5p/miR-195-5p, that showed high discriminatory performance for invasive ductal breast carcinoma in a discovery case-control cohort and an independent serum cohort. The findings, summarized from the article abstract, support further evaluation of the signature but do not establish its performance in prospective screening or establish clinical utility.

For the discovery analysis, the researchers measured the serum expression of 21 candidate circulating microRNAs by RT-qPCR in 46 treatment-naive patients with invasive ductal breast carcinoma and 46 healthy controls. Twelve candidates were significantly dysregulated after false-discovery-rate correction. miR-6838-5p and miR-195-5p produced the strongest discrimination individually and were combined in a two-miRNA logistic regression model. The model achieved an area under the receiver operating characteristic curve, or AUC, of 0.923 in the discovery cohort, with a 95% confidence interval of 0.873 to 0.974. An optimism-corrected AUC of 0.917 was obtained after 1,000 bootstrap iterations.

The investigators subsequently evaluated the same two-miRNA combination in the independent GSE73002 serum cohort, which contained 1,280 breast cancer patients and 2,684 non-cancer controls. In that dataset, the combination retained strong ROC-derived discriminatory performance, with an AUC of 0.939 and a 95% confidence interval of 0.930 to 0.948. The study also assessed whole-blood expression of four immune checkpoint-related genes—PDCD1, CD274, CTLA4 and LAG3—in 50 patients and 46 controls. The abstract describes exploratory downstream analyses as providing additional biological context but does not report their detailed results.

According to the abstract, the miR-6838-5p/miR-195-5p combination is a promising circulating miRNA signature for invasive ductal breast carcinoma. Its reported performance was consistent across the discovery sample and the independent serum cohort, although the study design and populations do not demonstrate that the signature can replace established diagnostic methods or support population screening. The authors called for evaluation in larger prospective studies and in clinically diverse cohorts that include people with benign breast disease and early-stage cancer. Paired serum–tissue studies and functional validation were also identified as necessary to clarify the signature’s clinical applicability and biological origin.

Subject of Research: Evaluation of a two-microRNA serum signature for discriminating invasive ductal breast carcinoma from healthy and non-cancer controls

Article Title: Identification of a circulating miR-6838-5p/miR-195-5p signature in invasive ductal breast carcinoma

Article References: Zeytunlu, M. B., Duzdag, F. E. I., Esin, H., Aktan, C., & Kaymaz, B. T. (2026). Identification of a circulating miR-6838-5p/miR-195-5p signature in invasive ductal breast carcinoma. Molecular Biology Reports, 53(1), Article 1584. https://doi.org/10.1007/s11033-026-12762-2

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12762-2

Keywords: invasive ductal breast carcinoma, circulating microRNAs, miR-6838-5p, miR-195-5p, serum biomarkers, case-control study, ROC analysis, model validation, GSE73002, Identification, circulating, signature