Bera Alakesh, Russ Eric, Manoharan Muthu Saravanan, Eidelman Ofer, Eklund Michael, Hueman Matthew, Pollard Harvey B, Hu Hai, Shriver Craig D, Srivastava Meera
Department of Anatomy, Physiology, and Genetics, Uniformed Services University Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814.
Department of Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229.
Mil Med. 2020 Jan 7;185(Suppl 1):669-675. doi: 10.1093/milmed/usz254.
Breast cancer is the most frequent cancer detected for women, and while our ability to treat breast cancer has improved substantially over the years, recurrence remains a major obstacle. Standard screening for new and recurrent breast cancer involves clinical breast imaging. However, there is no clinically approved noninvasive body fluid test for the early detection of recurrent breast cancer. Materials and Method: In this study, we analyzed serum samples from both recurrent and nonrecurrent breast cancer patients by different proteomics methods to identify biomarkers in patients with recurrence of disease.
Comparative data analysis identified several histone deacetylase (HDAC) proteins, which were found at significantly higher levels in the serum of recurrent breast cancer patients: HDAC9 (C-term) (P = 0.0035), HDAC5 (C-term) (P = 0.013), small ubiquitin-like modifier 1 (N-term) (P = 0.017), embryonic stem cell-expressed Ras (inter) (P = 0.018), and HDAC7 (C-term) (P = 0.020). Chronic inflammation plays a critical role in the development of the breast cancer recurrence, and we identified several proinflammatory cytokines that were present at elevated levels only in recurrent breast cancer patient serum.
Our data indicated that the epigenetic regulation of inflammatory processes plays a critical role in breast cancer recurrence. The identified proteins could lay the groundwork for the development of a serum-based breast cancer recurrence assay.
乳腺癌是女性中最常检测出的癌症，尽管多年来我们治疗乳腺癌的能力有了显著提高，但复发仍然是一个主要障碍。对新发和复发性乳腺癌的标准筛查包括临床乳腺成像。然而，目前尚无临床批准的用于早期检测复发性乳腺癌的非侵入性体液检测方法。材料与方法：在本研究中，我们通过不同的蛋白质组学方法分析了复发性和非复发性乳腺癌患者的血清样本，以鉴定疾病复发患者中的生物标志物。
比较数据分析确定了几种组蛋白去乙酰化酶（HDAC）蛋白，这些蛋白在复发性乳腺癌患者血清中的水平显著更高：HDAC9（C端）（P = 0.0035）、HDAC5（C端）（P = 0.013）、小泛素样修饰物1（N端）（P = 0.017）、胚胎干细胞表达的Ras（中间）（P = 0.018）和HDAC7（C端）（P = 0.020）。慢性炎症在乳腺癌复发的发展中起关键作用，我们鉴定了几种仅在复发性乳腺癌患者血清中水平升高的促炎细胞因子。
我们的数据表明，炎症过程的表观遗传调控在乳腺癌复发中起关键作用。所鉴定的蛋白质可为基于血清的乳腺癌复发检测方法的开发奠定基础。
