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综合分析揭示泛癌中突触结合蛋白样 4 的免疫和临床预后价值。

Integrated analysis unraveling the immunologic and clinical prognostic values of synaptotagmin like 4 in pan-cancer.

作者信息

Ren Yuehan, Wu Xiangbin, Li Jinlei, Zhou Zhenhua, Ni Shichang, Cai Jianhui

机构信息

Colorectal and Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Discov Oncol. 2025 Jun 6;16(1):1018. doi: 10.1007/s12672-025-02745-3.

Abstract

SYTL4 (Synaptotagmin Like 4) encodes a protein of synaptotagmin like protein family, which participates in intracellular membrane trafficking. Currently, its role and mechanisms in cancer remain unveiled, necessitating additional comprehensive analysis across different types of cancer to assess its potential in diagnosis, prognosis, chemotherapy, and immunotherapy in cancer. In our study, the mRNA level, threshold for copy number alterations, segmentation of masked copy number alterations, and methylation of SYTL4 DNA were analyzed based on data from TCGA pan-cancer cohort. miRNA, TCPA, mutation and clinical data were analyzed to evaluate diagnostic and prognostic significances of SYTL4. Then the results were checked using cBioPortal and GEO database. The protein levels were analyzed and evaluated based on HPA database and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Biological roles of SYTL4 in pan-cancer were explored by GSEA. We use multiple immune infiltration algorithms in TIMER2.0 and TISCH database to cross-verify the associations between SYTL4 expression and tumor immune microenvironment. Additionally, we depicted a pan-cancer survival map and explored the differences of gene expressions among cancers with different molecular subtypes. Through chemotherapy data from CellMiner, GDSC, CTRP database, we clarified the relationship between SYTL4 and drug resistance. Finally, we explored the chemical substances that affect SYTL4 expression through CTD database. This study systematically and comprehensively reveals the functions of SYTL4 and potential clinical diagnostic and therapeutic predictive values of SYTL4 in pan-cancer.

摘要

SYTL4(突触结合蛋白样4)编码一种突触结合蛋白样蛋白家族的蛋白质,其参与细胞内膜运输。目前,它在癌症中的作用和机制仍不明确,需要对不同类型的癌症进行额外的综合分析,以评估其在癌症诊断、预后、化疗和免疫治疗中的潜力。在我们的研究中,基于来自TCGA泛癌队列的数据,分析了SYTL4的mRNA水平、拷贝数改变阈值、隐蔽拷贝数改变的分割以及SYTL4 DNA的甲基化情况。分析了miRNA、TCPA、突变和临床数据,以评估SYTL4的诊断和预后意义。然后使用cBioPortal和GEO数据库对结果进行核对。基于HPA数据库和临床蛋白质组肿瘤分析联盟(CPTAC)对蛋白质水平进行了分析和评估。通过基因集富集分析(GSEA)探索了SYTL4在泛癌中的生物学作用。我们在TIMER2.0和TISCH数据库中使用多种免疫浸润算法来交叉验证SYTL4表达与肿瘤免疫微环境之间的关联。此外,我们绘制了泛癌生存图,并探索了不同分子亚型癌症之间基因表达的差异。通过来自CellMiner、GDSC、CTRP数据库的化疗数据,我们阐明了SYTL4与耐药性之间的关系。最后,我们通过CTD数据库探索了影响SYTL4表达的化学物质。本研究系统全面地揭示了SYTL4的功能以及SYTL4在泛癌中的潜在临床诊断和治疗预测价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c56f/12144028/d750ffe06e62/12672_2025_2745_Fig1_HTML.jpg

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