SMYD家族成员作为潜在的预后标志物，与胃癌中的免疫浸润相关。

SMYD Family Members Serve as Potential Prognostic Markers and Correlate with Immune Infiltrates in Gastric Cancer.

作者信息

Liu Donghui, Liu Menglin, Wang Wenxin, Li Xiaoxue, Shi Enhong, Zhang Chenyao, Wang Yinghui, Zhang Yan, Wang Liru, Wang Xuyao

机构信息

School of Life Science and Technology, Harbin Institute of Technology, Harbin 150000, Heilongjiang Province, China.

Department of Oncology, Heilongjiang Provincial Hospital, Harbin 150000, Heilongjiang Province, China.

出版信息

J Oncol. 2023 Feb 7;2023:6032864. doi: 10.1155/2023/6032864. eCollection 2023.

DOI:10.1155/2023/6032864

PMID:36816359

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9929213/

Abstract

BACKGROUND

The SMYD family comprises a group of genes encoding lysine methyltransferases, which are closely related to tumorigenesis. However, a systematic understanding of their role in gastric cancer (GC) is lacking.

METHODS

Using databases and tools such as the Cancer Genome Atlas, Human Protein Atlas, Kaplan-Meier Plotter, Gene Expression Profiling Interactive Analysis, and Metascape, we comprehensively analyzed differences in SMYD expression and its prognostic value as well as the association of SMYDs with immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). We conducted functional enrichment analysis and explored a competing endogenous RNA mechanism regulating SMYD mRNA and protein levels in patients with GC.

RESULTS

In GC, the expression of SMYD2/3/4/5 mRNA was significantly upregulated, as opposed to that of mRNA, which was significantly downregulated. The protein levels of SMYDs were consistent with mRNA levels. SMYD1/2/4/5 was negatively correlated with overall survival; SMYD1/2/3/5 was negatively correlated with progression-free survival. Our SMYD-based signature and nomogram model may be useful for inferring the prognosis of GC. All SMYDs were closely associated with the infiltration of six immune cell types: uncharacterized, CD8 , CD4 , macrophage, endothelial, and B cells. TMB was significantly negatively correlated with SMYD1 expression, while a significant positive correlation was observed with SMYD2/5. Furthermore, MSI was significantly positively correlated with SMYD2/5 expression. Long non-coding RNAs, such as chr22-38_28785274-29006793.1, XLOC_002309, and CTD-2008N3.1, were suggested to regulate SMYD expression by sponging multiple microRNAs.

CONCLUSION

SMYDs are differentially expressed in GC and are thus potential prognostic markers. SMYD expression is closely related to immune infiltration, TMB, and MSI, all of which are closely related to the response to targeted immune therapy.

摘要

背景

SMYD家族由一组编码赖氨酸甲基转移酶的基因组成，这些基因与肿瘤发生密切相关。然而，目前缺乏对它们在胃癌（GC）中作用的系统认识。

方法

我们使用癌症基因组图谱、人类蛋白质图谱、Kaplan-Meier Plotter、基因表达谱交互分析和Metascape等数据库和工具，全面分析了SMYD表达的差异及其预后价值，以及SMYDs与免疫细胞浸润、肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）的关联。我们进行了功能富集分析，并探索了一种竞争性内源性RNA机制，该机制在GC患者中调节SMYD mRNA和蛋白质水平。

结果

在GC中，SMYD2/3/4/5 mRNA的表达显著上调，而mRNA的表达则显著下调。SMYDs的蛋白质水平与mRNA水平一致。SMYD1/2/4/5与总生存期呈负相关；SMYD1/2/3/5与无进展生存期呈负相关。我们基于SMYD的特征和列线图模型可能有助于推断GC的预后。所有SMYDs都与六种免疫细胞类型的浸润密切相关：未分类的、CD8、CD4、巨噬细胞、内皮细胞和B细胞。TMB与SMYD1表达呈显著负相关，而与SMYD2/5呈显著正相关。此外，MSI与SMYD2/5表达呈显著正相关。长链非编码RNA，如chr22-38_28785274-29006793.1、XLOC_002309和CTD-2008N3.1，被认为通过海绵化多种微小RNA来调节SMYD表达。