Table1_Prognostic Potential of Secreted Modular Calcium-Binding Protein 1 in Low-Grade Glioma.XLSX

Background: Secreted modular calcium-binding protein 1 (SMOC1) belongs to a family of matricellular proteins; it was involved in embryo development, endothelial cell proliferation, angiogenesis, integrin–matrix interactions, cell adhesion, and regulation of glucose metabolism. Previous studies showed that the expression of SMOC1 was increased in some tumors. However, the prognostic value and the biological function of SMOC1 in tumor remain unclear.Methods: In this study, we explored the expression profile and prognostic value of SMOC1 in pan-cancers, especially glioma, via multiple databases, including Oncomine, Gene Expression Profiling Interactive 2, PrognoScan, Kaplan–Meier plotter, and the Chinese Glioma Genome Atlas database. Furthermore, LinkedOmics was used to identify the genes coexpressed with SMOC1 and to perform Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology analysis in low-grade glioma (LGG). Also, the Cancer Single-Cell State Atlas database was used to evaluate the correlation between SMOC1 expression and functional state activities in glioma cells. In addition, the Tumor Immune Estimation Resource and TISIDB databases were used to evaluate the correlations between SMOC1 expression and tumor-infiltrating immune cells in the tumor microenvironment.Results: Compared with normal brain tissues, the expression of SMOC1 was increased in LGG tissues. The higher expression of SMOC1 was significantly correlated with better survival of LGG patients. Additionally, functional analyses showed that the SMOC1 coexpressed genes were inhibited in processes such as response to type I interferon and interferon-gamma, lymphocyte-mediated immunity, leukocyte migration, adaptive immune response, neutrophil-mediated immunity, T cell activation, and pathways including EMC–receptor interaction, Th17 cell differentiation, and leukocyte trans-endothelial migration in LGG. Moreover, the expression of SMOC1 was correlated with stemness, hypoxia, EMT, and metastasis of glioma cells. Additionally, the expression of SMOC1 expression was negatively correlated with levels of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells, and gene markers of most immune cells in LGG.Conclusion: Our results suggest that SMOC1 could be a potential biomarker to determine prognosis and might play a specific role in the tumor microenvironment of glioma, thereby influencing the development and progression of glioma. These findings provide some new insights for further investigation.

背景：分泌型模块化钙结合蛋白1（SMOC1）属于基质细胞蛋白家族；其在胚胎发育、内皮细胞增殖、血管生成、整合素-基质相互作用、细胞粘附以及葡萄糖代谢的调节中发挥作用。既往研究表明，SMOC1的表达在某些肿瘤中有所增加。然而，SMOC1在肿瘤中的预后价值和生物学功能尚不明确。方法：在本研究中，我们通过多个数据库，包括Oncomine、Gene Expression Profiling Interactive 2、PrognoScan、Kaplan–Meier plotter以及中国胶质瘤基因组图谱数据库，探讨了SMOC1在泛癌，尤其是胶质瘤中的表达谱和预后价值。此外，利用LinkedOmics数据库鉴定与SMOC1共表达的基因，并在低级别胶质瘤（LGG）中执行京都基因与基因途径和基因本体分析。同时，利用Cancer Single-Cell State Atlas数据库评估SMOC1表达与胶质瘤细胞功能状态活动之间的相关性。另外，使用Tumor Immune Estimation Resource和TISIDB数据库评估SMOC1表达与肿瘤微环境中肿瘤浸润免疫细胞的相关性。结果：与正常脑组织相比，LGG组织中SMOC1的表达增加。SMOC1的高表达与LGG患者的良好预后显著相关。此外，功能分析显示，SMOC1共表达的基因在诸如对I型干扰素和干扰素-γ的反应、淋巴细胞介导的免疫、白细胞迁移、适应性免疫反应、中性粒细胞介导的免疫、T细胞活化等过程中受到抑制，并在LGG中涉及EMC-受体相互作用、Th17细胞分化以及白细胞跨内皮迁移等途径。此外，SMOC1的表达与胶质瘤细胞的干性、缺氧、EMT和转移相关。另外，SMOC1的表达与浸润B细胞、CD8+ T细胞、CD4+ T细胞、巨噬细胞、中性粒细胞和树突状细胞的比例呈负相关，以及LGG中大多数免疫细胞的基因标志物。结论：我们的研究结果表明，SMOC1可能成为确定预后的潜在生物标志物，并在胶质瘤的肿瘤微环境中发挥特定的作用，从而影响胶质瘤的发展和进展。这些发现为进一步的调查研究提供了一些新的见解。