Abstract
BackgroundAlthough 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.MethodsWe 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.ResultsAmong 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 χ2 = 16.13; p < 0.001). Among the patients that received no radiotherapy (156/238), SNCG status was not correlated with OS (log rank χ2 = 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.ConclusionA 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2750-y) contains supplementary material, which is available to authorized users.
Highlights
Radiotherapy following mastectomy was demonstrated to reduce the recurring risk and improve the prognosis of patients with breast cancer, it is notorious for comprehensive side effects, only a selected group of patients can benefit
For patients treated with radiotherapy or not, there were no significant associations between SNCG expression and Age (p = 0.767, 0.665), Tumor size (p = 0.145, 0.142), Metastasis lymph node (p = 0.117, 0.332), TNM stage (p = 0.428, 0.957), Estrogen receptor (ER) status (p = 0.304, 0.998), PR status (p = 0.171, 0.904), or HER2 status (p = 0.351, 0.646), and all of the clinicopathologic features in both subgroups were distributed (Table 1)
Relationship between SNCG expression and radiotherapy stratified survival Positive SNCG was correlated with decreased overall survival (OS) and distant metastasis-free survival (DMFS) in breast cancer patients, regardless of the utilization or non-utilization of radiotherapy
Summary
Radiotherapy following mastectomy was demonstrated to reduce the recurring risk and improve the prognosis of patients with breast cancer, it is notorious for comprehensive side effects, only a selected group of patients can benefit. Radiotherapy is associated with potential long-term side effects and radiation oncologists have to be highly selective of patients and administer radiation treatments with extreme caution [6, 7]. Despite such precautions, not every patient subjected to radiotherapy can benefit from it. Biomarkers capable of predicting radiotherapeutic efficacy would largely strengthen current clinical options by providing instructions for appropriate risk evaluation and treatment plan selection
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