Wu Xuanang, Gao Bo, Xiao Kun, Saleem Nimra
Neuroscience Research Center, Institute of Mitochondrial Biology and Medicine, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710000, Shaanxi, China.
Department of Sports, Shaanxi Polytechnic Institute, Xianyang, 712000, Shaanxi, China.
Neuromolecular Med. 2025 Jul 17;27(1):52. doi: 10.1007/s12017-025-08873-x.
Synaptotagmins (Syts) are a family of crucial Ca sensors for cellular secretions, while half of the Syt isoforms are evolutionarily non-Ca-affinitive, which are less studied but associated with several neuro-system diseases. Some Syt isoforms exhibited importance in specific cancer types, but a comprehensive study of all Syts in pan-cancer is lacking. Here, using informatics tools and proteome/transcriptome databases, the expression, phosphorylation, CpG methylation profiles, and the correlation with genome heterogeneity, tumor stemness, and immune infiltration of all human Syts are analyzed in human pan-cancer, resulting in significant associations of each Syt in various types of cancer, including pathological stage and prognosis. Most Syts exhibit noteworthy expression level changes in GBM/LGG and PCPG, and Syt11 has a strong association with immune infiltration. The Ca-affinitive and non-Ca-affinitive Syt groups show opposite changes in both expression and methylation levels in an overview scale suggesting different mechanisms of them in cancers. Detection of similar expression genes suggests that Ca-affinitive Syts may participate in the RNA-splicing process, while non-Ca-affinitive Syts are involved in NF-κB signaling and immune regulation. This study uncovers the clinical potential of each Syt isoform and discusses clues to their roles, such as Ca sensitivity and immune regulation, in tumor progression. The overall data are informative for future refining and mining.
突触结合蛋白（Syts）是细胞分泌过程中至关重要的钙传感器家族，而一半的Syt亚型在进化上对钙不敏感，对其研究较少，但与几种神经系统疾病相关。一些Syt亚型在特定癌症类型中表现出重要性，但缺乏对泛癌中所有Syt的全面研究。在这里，利用信息学工具和蛋白质组/转录组数据库，在人类泛癌中分析了所有人类Syt的表达、磷酸化、CpG甲基化谱，以及与基因组异质性、肿瘤干性和免疫浸润的相关性，结果显示每种Syt在各种类型癌症中都有显著关联，包括病理分期和预后。大多数Syt在胶质母细胞瘤/低级别胶质瘤（GBM/LGG）和嗜铬细胞瘤（PCPG）中表现出值得注意的表达水平变化，并且Syt11与免疫浸润密切相关。总体而言，对钙敏感和对钙不敏感的Syt组在表达和甲基化水平上呈现相反的变化，这表明它们在癌症中的作用机制不同。检测相似表达基因表明，对钙敏感的Syt可能参与RNA剪接过程，而对钙不敏感的Syt则参与核因子κB（NF-κB）信号传导和免疫调节。本研究揭示了每种Syt亚型的临床潜力，并讨论了它们在肿瘤进展中的作用线索，如钙敏感性和免疫调节。总体数据为未来的细化和挖掘提供了信息。
