Identification of PHB2 as a Potential Biomarker of Luminal A Breast Cancer Cells Using a Cell-Specific Aptamer

Precise diagnosis of breast cancer molecular subtypes remains a great challenge in clinics. The present molecular biomarkers are not specific enough to classify breast cancer subtypes precisely, which requests for more accurate and specific molecular biomarkers to be discovered. Aptamers evolved by the cell-systematic evolution of ligands by exponential enrichment (SELEX) method show great potential in the discovery and identification of cell membrane targets via aptamer-based cell membrane protein pull-down, which has been regarded as a novel and powerful weapon for the discovery and identification of new molecular biomarkers. Herein, a cell membrane protein PHB2 was identified as a potential molecular biomarker specifically expressed in the cell membranes of MCF-7 breast cancer cells using a DNA aptamer MF3Ec. Further experiments demonstrated that the PHB2 protein is differentially expressed in the cell membranes of MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cells and MCF-10A cells, and the binding molecular domains of aptamer MF3Ec and anti-PHB2 antibodies to the PHB2 protein are different due to there being no obvious competitions between aptamer MF3Ec and anti-PHB2 antibodies in the binding to the cell membranes of target MCF-7 cells. Due to those four cells belonging to luminal A, HER2-positive, and triple-negative breast cancer cell subtypes and human normal mammary epithelial cells, respectively, the PHB2 protein in the cell membrane may be a potential biomarker for precise diagnosis of the luminal A breast cancer cell subtype, which is endowed with the ability to differentiate the luminal A breast cancer cell subtype from HER2-positive and triple-negative breast cancer cell subtypes and human normal mammary epithelial cells, providing a new molecular biomarker and therapeutic target for the accurate and precise classification and diagnostics and personalized therapy of breast cancer.