Min Li, Zhang Cheng, Ma Ruolan, Li Xiaofan, Yuan Hua, Li Yihao, Chen Ruxuan, Liu Caiyun, Guo Jianping, Qu Like, Shou Chengchao
Department of Biochemistry and Molecular Biology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, 100142, China.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA, 02115, USA.
BMC Cancer. 2016 Sep 5;16(1):717. doi: 10.1186/s12885-016-2750-y.
Although radiotherapy following mastectomy was demonstrated to reduce the recurring risk and improve the prognosis of patients with breast cancer, it is also notorious for comprehensive side effects, hence only a selected group of patients can benefit. Therefore, the screening of molecular markers capable of predicting the efficacy of radiotherapy is essential.
We have established a cohort of 454 breast cancer cases and selected 238 patients with indications for postoperative radiotherapy. Synuclein-γ (SNCG) protein levels were assessed by immunohistochemistry, and SNCG status was retrospectively correlated with clinical features and survival in patients treated or not treated with radiotherapy. Gene Set Enrichment Analysis (GSEA) and survival analysis for online datasets were also performed for further validation.
Among patients that received radiotherapy (82/238), those demonstrating positive SNCG expression had a 55.0 month shorter median overall survival (OS) in comparison to those demonstrating negative SNCG expression (78.4 vs. 133.4 months, log rank χ (2) = 16.13; p < 0.001). Among the patients that received no radiotherapy (156/238), SNCG status was not correlated with OS (log rank χ (2) = 2.40; p = 0.121). A COX proportional hazard analysis confirmed SNCG as an independent predictor of OS, only for patients who have received radiotherapy. Similar results were also obtained for distant metastasis-free survival (DMFS). A GSEA analysis indicated that SNCG was strongly associated with genes related to a radiation stress response. A survival analysis was performed with online databases consisting of breast cancer, lung cancer, and glioblastoma and further confirmed SNCG's significance in predicting the survival of patients that have received radiotherapy.
A positive SNCG may serve as a potential marker to identify breast cancer patients who are less likely to benefit from radiotherapy and may also be extended to other types of cancer. However, the role of SNCG in radiotherapy response still needs to be further validated in randomized controlled trials prior to being exploited in clinical practice.
尽管乳房切除术后放疗被证明可降低乳腺癌患者的复发风险并改善预后，但它也因综合副作用而声名狼藉，因此只有部分特定患者能从中受益。所以，筛选能够预测放疗疗效的分子标志物至关重要。
我们建立了一个包含454例乳腺癌病例的队列，并挑选出238例有术后放疗指征的患者。通过免疫组织化学评估突触核蛋白γ（SNCG）蛋白水平，并回顾性分析SNCG状态与接受或未接受放疗患者的临床特征及生存情况的相关性。还进行了基因集富集分析（GSEA）以及对在线数据集的生存分析以作进一步验证。
在接受放疗的患者中（82/238），SNCG表达呈阳性的患者中位总生存期（OS）比SNCG表达呈阴性的患者短55.0个月（78.4个月对133.4个月，对数秩检验χ(2)=16.13；p<0.001）。在未接受放疗的患者中（156/238），SNCG状态与OS无相关性（对数秩检验χ(2)=2.40；p=0.121）。COX比例风险分析证实，仅对于接受放疗的患者，SNCG是OS的独立预测因子。远处无转移生存期（DMFS）也得到了类似结果。GSEA分析表明，SNCG与辐射应激反应相关基因密切相关。对包含乳腺癌、肺癌和胶质母细胞瘤的在线数据库进行生存分析，进一步证实了SNCG在预测接受放疗患者生存情况方面的意义。
SNCG阳性可能作为一种潜在标志物，用于识别不太可能从放疗中受益的乳腺癌患者，并且这一作用可能也适用于其他类型癌症。然而，SNCG在放疗反应中的作用在临床实践应用前仍需在随机对照试验中进一步验证。
