Comprehensive Analysis of the Value of SMYD Family Members in the Prognosis and Immune Infiltration of Malignant Digestive System Tumors

Liu, Donghui; Wang, Xuyao; Shi, Enhong; Wang, Liru; Nie, Minghao; Li, Long; Jiang, Qingxin; Kong, Pengyu; Shi, Shuai; Wang, Chao; Yan, Sen; Qin, Zhihui; Zhao, Shuang

doi:10.3389/fgene.2021.699910

Cited by 5 publications

(3 citation statements)

References 62 publications

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“…International Publisher infiltration of FoxP3+ regulatory T cells (Treg) in TME is a poor prognostic biomarker in HCC, but the densities of CD20+ B cells or CD57+ natural killer (NK) cells in HCC are positively related to the prognosis of HCC [8]. Furthermore, the correlation between genes that contribute to the prognosis of HCC and immune infiltration was investigated using transcriptomic data [9,10].…”

Section: Ivyspringmentioning

confidence: 99%

Identification of circadian clock genes as regulators of immune infiltration in Hepatocellular Carcinoma

Zhang¹,

Liang²,

Gao³

et al. 2022

J. Cancer

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Background: Multiple studies have reported that the immune system is under the control of a circadian clock, especially in cancers, but how circadian clock genes shape tumor immune cell infiltration in hepatocellular carcinoma (HCC) remains unclear. Methods: The rhythmicity of circadian clock genes was investigated using the GETx database. The expression and methylation level of circadian clock genes in HCC and paracancerous was evaluated using the GETx and TCGA databases. The differential expression of circadian clock genes in HCC was analyzed using the “limma” package of the R 4.0.4 software. The prognosis of each circadian clock gene was accessed by Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. Quantitative real-time PCR and immunohistochemistry (IHC) was carried out to confirm the results. The relationship between circadian rhythm and immune infiltration in HCC was evaluated using the TIMER database and the CIBERSORT algorithm. Results: In addition to RORA, RORB, and ARNTL2, there was a rhythmic expression of other circadian clock genes in liver tissue. The correlation between the expression of circadian clock genes differed when comparing HCC and liver tissue. HCC patients who express low levels of PER-1and CRY2 had a poor overall survival (OS). In contrast, patients with higher expression of NPAS2 had a poor prognosis. In HCC, the expression of the PER-1, CRY2, and NPAS2 genes was closely related to immune infiltration. Conclusion: Our study indicated the disruption of the expression of circadian clock-regulated genes in HCC and identified PER-1, CRY2, and NPAS2 as independent predictors of survival. These genes may be applied as candidate molecular targets for diagnosis and therapy of HCC.

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Section: Ivyspringmentioning

confidence: 99%

Identification of circadian clock genes as regulators of immune infiltration in Hepatocellular Carcinoma

Zhang¹,

Liang²,

Gao³

et al. 2022

J. Cancer

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“…These proteins contain the SET domain, responsible for lysine methylation. The SET domain is divided into two segments by the MYND domain (Myeloid, Nervy, and DEAF-1), which is a unique characteristic of the SMYD family that facilitates protein-protein interactions [ 3 ]. While SMYD4 has been less studied in carcinogenesis compared to other members of the SMYD family, it has been identified as a potential tumor suppressor due to its observed downregulation in breast cancer [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Alterations of SMYD4 in Solid Tumors Using Integrative Multi-Platform Analysis

Olivera Santana,

de Loyola,

Gualberto

et al. 2024

IJMS

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SMYD4 is a member of the SMYD family that has lysine methyltransferase function. Little is known about the roles of SMYD4 in cancer. The aim of this study is to investigate genetic alterations in the SMYD4 gene across the most prevalent solid tumors and determine its potential as a biomarker. We performed an integrative multi-platform analysis of the most common mutations, copy number alterations (CNAs), and mRNA expression levels of the SMYD family genes using cohorts available at the Cancer Genome Atlas (TCGA), cBioPortal, and the Catalogue of Somatic Mutations in Cancer (COSMIC). SMYD genes displayed a lower frequency of mutations across the studied tumors, with none of the SMYD4 mutations detected demonstrating sufficient discriminatory power to serve as a biomarker. In terms of CNAs, SMYD4 consistently exhibited heterozygous loss and downregulation across all tumors evaluated. Moreover, SMYD4 showed low expression in tumor samples compared to normal samples, except for stomach adenocarcinoma. SMYD4 demonstrated a frequent negative correlation with other members of the SMYD family and a positive correlation between CNAs and mRNA expression. Additionally, patients with low SMYD4 expression in STAD and LUAD tumors exhibited significantly poorer overall survival. SMYD4 demonstrated its role as a tumor suppressor in the majority of tumors evaluated. The consistent downregulation of SMYD4, coupled with its association with cancer progression, underscores its potential usefulness as a biomarker.

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“…SMYD4 has been identified as a tumor suppressor gene in breast cancer [ 18 ], and SMYD5 may be involved in cancer and stem cell maintenance [ 19 , 20 ]. Finally, several studies have suggested the association of SMYDs with immune infiltration in breast cancer and digestive system malignancies [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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

Liu

Wang

et al. 2023

Journal of Oncology

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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 SMYD1 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+T, CD4+T, 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.

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Comprehensive Analysis of the Value of SMYD Family Members in the Prognosis and Immune Infiltration of Malignant Digestive System Tumors

Cited by 5 publications

References 62 publications

Identification of circadian clock genes as regulators of immune infiltration in Hepatocellular Carcinoma

Identification of circadian clock genes as regulators of immune infiltration in Hepatocellular Carcinoma

Genetic Alterations of SMYD4 in Solid Tumors Using Integrative Multi-Platform Analysis

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

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