Wu Kejin, Quan Zhiwei, Weng Ziyi, Li Fangming, Zhang Yichu, Yao Xiaohong, Chen Yiding, Budman Daniel, Goldberg Itzhak D, Shi Y Eric
Department of General Surgery, XinHua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
Breast Cancer Res Treat. 2007 Mar;101(3):259-67. doi: 10.1007/s10549-006-9296-7. Epub 2006 Jul 4.
Synucleins are emerging as central players in the fundamental neural processes and in the formation of pathologically insoluble deposits characteristic of neurodegenerative diseases. However, synuclein gamma (SNCG), previously identified as a breast cancer specific gene (BCSG1), is also highly expressed in breast carcinomas, but not expressed in normal or benign breast tissues. We analyzed SNCG gene expression in 93 clinical breast specimens and associated it with clinical outcome. Overall SNCG mRNA expression was detectable in 36% breast cancers. However, 81% of stage III/IV breast cancers were positive for SNCG expression, while only 15% of stage I/II breast cancers were positive for SNCG expression. In contrast, SNCG was undetectable in benign breast lesions. Expression of SNCG in the primary tumor also significantly associated with lymph node involvement and metastasis. There was no significant correlation between SNCG gene expression and age, menstruation, and status of ER, PR, PCNA, and HER-2. Patients whose tumors expressed SNCG had a significantly shorter DFS and a high probability of death when compared with those whose tumors did not express SNCG. The hazard ratio of metastasis or recurrence according to the SNCG status was 4.515 (95% CI, 1,188-17.154; P = 0.027). Cox multivariate analysis showed that SNCG had independent prognostic significance above and beyond conventional variables. This study suggests that the expression of SNCG is an independent predictive marker for recurrence and metastasis in breast cancer progression. SNCG is expected to be a useful marker for breast cancer progression and a potential target for breast cancer treatment.
突触核蛋白正逐渐成为神经基本过程以及神经退行性疾病特征性病理不溶性沉积物形成中的核心参与者。然而,γ-突触核蛋白(SNCG),先前被鉴定为乳腺癌特异性基因(BCSG1),在乳腺癌中也高度表达,但在正常或良性乳腺组织中不表达。我们分析了93例临床乳腺标本中SNCG基因的表达情况,并将其与临床结果相关联。总体而言,36%的乳腺癌中可检测到SNCG mRNA表达。然而,81%的III/IV期乳腺癌SNCG表达呈阳性,而只有15%的I/II期乳腺癌SNCG表达呈阳性。相比之下,良性乳腺病变中未检测到SNCG。SNCG在原发性肿瘤中的表达也与淋巴结受累和转移显著相关。SNCG基因表达与年龄、月经以及雌激素受体(ER)、孕激素受体(PR)、增殖细胞核抗原(PCNA)和人表皮生长因子受体2(HER-2)的状态之间无显著相关性。与肿瘤未表达SNCG的患者相比,肿瘤表达SNCG的患者无病生存期显著缩短,死亡概率更高。根据SNCG状态,转移或复发的风险比为4.515(95%置信区间,1.188 - 17.154;P = 0.027)。Cox多因素分析表明,SNCG具有超越传统变量的独立预后意义。本研究表明,SNCG的表达是乳腺癌进展中复发和转移的独立预测标志物。SNCG有望成为乳腺癌进展的有用标志物以及乳腺癌治疗的潜在靶点。