Li Deheng, Li Liangdong, Yang Wentao, Chen Lei, Chen Xin, Wang Qifeng, Hao Bin, Jin Wei, Cao Yiqun
Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Ann Transl Med. 2020 Aug;8(15):922. doi: 10.21037/atm-20-681.
Breast cancer (BC) is one of the most lethal malignant tumors and the leading cause of cancer-related death worldwide. Although early diagnostic techniques for BC have been well developed, 40% of cases are still diagnosed at the advanced stage, while for BC patients with distant metastases, the 5-year survival rate is usually lower than 30%. The Snail family, generally regarded as transcriptional repressors, has been indicated to be an essential prognostic factor in malignant tumors. However, limited data exist on public databases concerning the prognostic value of individual Snail family members in BC, especially SNAI3.
Data from public databases including cBioPortal for Cancer Genomics, Gene Expression Omnibus, UCSC Xena Browser, and Human Protein Atlas (HPA) were downloaded. Based on the Kaplan¬-Meier plotter platform, correlation of the three members of the Snail family and prognosis in BC were analyzed. Individual Snail family members and their co-expressed genes were respectively enriched on different pathways and biological processes via the functional enrichment analysis (FunRich) tool.
High SNAI1 mRNA expression was associated with shorter distant metastasis-free survival (DMFS) in all BC patients regardless of PAM50 subtype. Conversely, high SNAI3 mRNA expression was associated with longer DMFS. Although the presence of SNAI2 expression was significantly associated with DMFS in the whole cohort, no significant correlation was found in patients with luminal A or HER2 subtype. For patients with the most diverse clinicopathological features, high SNAI1 expression was associated with poor survival, with the converse being true for SNAI3. However, the impact on prognosis of patients with different clinicopathological features produced by SNAI2 expression was inconclusive. Furthermore, we discovered that SNAI1 or SNAI2 and their co-expressed genes frequently enriched receptor tyrosine kinase (RTK) signaling and integrin-related pathways which mainly functioned on epithelial-mesenchymal transition and were further involved in several processes of signal transduction and cell communication. Furthermore, as SNAI3, along with its co-expressed genes, enriched immune-related pathways, it may thus play a role in mediating the immune system.
Our analysis revealed that SNAI1 mRNA expression may potentially be a negative prognostic factor, whereas SNAI3 mRNA was associated with positive prognosis in BC. Therefore, the assessment of SNAI1 and SNAI3 expression may be valuable for predicting prognosis in BC patients.
乳腺癌（BC）是最致命的恶性肿瘤之一，也是全球癌症相关死亡的主要原因。尽管BC的早期诊断技术已得到很好的发展，但仍有40%的病例在晚期才被诊断出来，而对于有远处转移的BC患者，5年生存率通常低于30%。Snail家族通常被认为是转录抑制因子，已被证明是恶性肿瘤的一个重要预后因素。然而，公共数据库中关于Snail家族单个成员在BC中的预后价值的数据有限，尤其是SNAI3。
下载来自癌症基因组学cBioPortal、基因表达综合数据库（Gene Expression Omnibus）、加州大学圣克鲁兹分校Xena浏览器（UCSC Xena Browser）和人类蛋白质图谱（Human Protein Atlas，HPA）等公共数据库的数据。基于Kaplan-Meier绘图平台，分析Snail家族三个成员与BC预后的相关性。通过功能富集分析（FunRich）工具，将Snail家族单个成员及其共表达基因分别富集到不同的途径和生物学过程中。
无论PAM50亚型如何，在所有BC患者中，高SNAI1 mRNA表达与较短的无远处转移生存期（DMFS）相关。相反，高SNAI3 mRNA表达与较长的DMFS相关。虽然在整个队列中，SNAI2表达的存在与DMFS显著相关，但在腔面A型或HER2亚型患者中未发现显著相关性。对于具有最多样化临床病理特征的患者，高SNAI1表达与不良生存相关，而SNAI3则相反。然而，SNAI2表达对不同临床病理特征患者预后的影响尚无定论。此外，我们发现SNAI1或SNAI2及其共表达基因经常富集受体酪氨酸激酶（RTK）信号传导和整合素相关途径，这些途径主要在上皮-间质转化中起作用，并进一步参与信号转导和细胞通讯的几个过程。此外，由于SNAI3与其共表达基因一起富集了免疫相关途径，因此它可能在介导免疫系统中发挥作用。
我们的分析表明，SNAI1 mRNA表达可能是一个负面预后因素，而SNAI3 mRNA与BC的阳性预后相关。因此，评估SNAI1和SNAI3的表达可能对预测BC患者的预后有价值。
