Guo Jianping, Shou Chengchao, Meng Lin, Jiang Beihai, Dong Bin, Yao Lihua, Xie Yuntao, Zhang Jianzhi, Chen Yiding, Budman Daniel R, Shi Yuenian Eric
Department of Radiation Oncology, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.
Int J Cancer. 2007 Sep 15;121(6):1296-305. doi: 10.1002/ijc.22763.
Synuclein gamma (SNCG), previously identified as a breast cancer-specific gene (BCSG1), is highly expressed in breast carcinomas but not in normal epithelium. SNCG regulates many pathways in growth and progression of breast cancer. To determine if SNCG is a biomarker for clinical prognosis of breast cancer, we generated a panel of murine monoclonal antibodies (mAbs) against human SNCG and correlated SNCG protein expression in 358 clinical breast cancer specimens with clinical outcome. A panel of 14 mAbs was characterized by ELISA, immunoprecipitation (IP), Western blot, immunocytochemistry and immunohistochemistry. SNCG protein expression was determined in 438 clinical breast specimens by immunohistochemical analysis using mAb 5C5. Expression of SNCG was strongly correlated with the stage, lymph node involvement, metastasis, tumor size and Her-2 status, but its expression was not associated with ER and PR expression status. While 71.4% of advanced breast cancers were positive for SNCG expression, only 26.8% of Stage I/II breast cancers were positive for SNCG expression and 5.2% of benign hyperplasia expressed SNCG. SNCG protein was not detectable in normal tissue adjacent to breast cancer. After a median follow-up of 64 months, patients with an SNCG-positive tumor had a significantly shorter disease-free survival and overall survival and a high probability of death compared no expression of SNCG. Multivariate analysis demonstrated that SNCG was a strong independent prognostic variable. SNCG is a new unfavorable prognostic marker for breast cancer progression and a potential target for breast cancer treatment.
γ-突触核蛋白（SNCG），先前被鉴定为乳腺癌特异性基因（BCSG1），在乳腺癌中高度表达，但在正常上皮组织中不表达。SNCG调节乳腺癌生长和进展的许多途径。为了确定SNCG是否为乳腺癌临床预后的生物标志物，我们制备了一组针对人SNCG的鼠单克隆抗体（mAb），并将358例临床乳腺癌标本中的SNCG蛋白表达与临床结果相关联。通过酶联免疫吸附测定（ELISA）、免疫沉淀（IP）、蛋白质印迹法、免疫细胞化学和免疫组织化学对一组14种mAb进行了表征。使用mAb 5C5通过免疫组织化学分析在438例临床乳腺标本中测定SNCG蛋白表达。SNCG的表达与分期、淋巴结受累情况、转移、肿瘤大小和Her-2状态密切相关，但其表达与雌激素受体（ER）和孕激素受体（PR）表达状态无关。虽然71.4%的晚期乳腺癌SNCG表达呈阳性，但只有26.8%的I/II期乳腺癌SNCG表达呈阳性，5.2%的良性增生表达SNCG。在乳腺癌旁的正常组织中未检测到SNCG蛋白。经过64个月的中位随访，SNCG阳性肿瘤患者的无病生存期和总生存期明显缩短，与SNCG无表达相比死亡概率更高。多变量分析表明，SNCG是一个强大的独立预后变量。SNCG是乳腺癌进展的一个新的不良预后标志物，也是乳腺癌治疗的一个潜在靶点。
