Mao Yukun, Hou Xueying, Fu Su, Luan Jie
Breast Plastic and Reconstructive Surgery Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100144, China.
Genes Dis. 2023 Sep 9;11(3):101087. doi: 10.1016/j.gendis.2023.101087. eCollection 2024 May.
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.
包膜挛缩是一种常见且严重的并发症，会影响接受硅胶乳房植入物患者的术后效果。目前，假体置换是隆胸手术和乳腺癌手术后乳房重建术后包膜挛缩的主要治疗方法。然而，乳房包膜挛缩的潜在机制仍不清楚。本研究旨在通过RNA测序确定乳房包膜挛缩的生物学特征并揭示潜在机制。根据贝克分级，将12名女性患者（15个乳房包膜）的样本组织分为低包膜挛缩（LCC）组和高包膜挛缩（HCC）组。随后，通过富集分析确定了41个脂质代谢相关基因，其中3个基因通过支持向量机递归特征消除法（SVM-RFE）和最小绝对收缩和选择算子（LASSO）算法被确定为候选基因。然后，我们使用CIBERSORT分析比较了LCC组和HCC组之间22种免疫细胞的比例，并探讨了候选核心特征与免疫细胞之间的相关性。值得注意的是，PRKAR2B与差异聚集的免疫细胞呈正相关，这些免疫细胞是M1巨噬细胞和滤泡辅助性T细胞（ROC曲线下面积=0.786）。此外，PRKAR2B在mRNA或蛋白质水平的表达在HCC组中低于LCC组。根据PRKAR2B高低表达组的表达水平确定了潜在的分子机制。我们的研究结果表明，PRKAR2B是一种新型的乳房包膜挛缩诊断生物标志物，也可能影响包膜挛缩的分级和进展。
