Capsular contracture is a prevalent and severe complication that affects the postoperative outcomes of patients who receive silicone breast implants. At present

prosthesis replacement is the major treatment for capsular contracture after both breast augmentation procedures and breast reconstruction following breast cancer surgery. However

the mechanism(s) underlying breast capsular contracture remains unclear. This study aimed to identify the biological features of breast capsular contracture and reveal the potential underlying mechanism using RNA sequencing. Sample tissues from 12 female patients (15 breast capsules) were divided into low capsular contracture (LCC) and high capsular contracture (HCC) groups based on the Baker grades. Subsequently

41 lipid metabolism-related genes were identified through enrichment analysis

and three of these genes were identified as candidate genes by SVM-RFE and LASSO algorithms. We then compared the proportions of the 22 types of immune cells between the LCC and HCC groups using a CIBERSORT analysis and explored the correlation between the candidate hub features and immune cells. Notably

PRKAR2B was positively correlated with the differentially clustered immune cells

which were M1 macrophages and follicular helper T cells (area under the ROC = 0.786). In addition

the expression of PRKAR2B at the mRNA or protein level was lower in the HCC group than in the LCC group. Potential molecular mechanisms were identified based on the expression levels in the high and low PRKAR2B groups. Our findings indicate that PRKAR2B is a novel diagnostic biomarker for breast capsular contracture and might also influence the grade and progression of capsular contracture.