SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma

Fan, Zhongyi; Duan, Jingjing; Luo, Pu; Shao, Ling; Chen, Qiong; Tan, Xiaohua; Zhang, Lei; Xu, Xiaojie

doi:10.1038/s41419-022-04718-8

Cited by 9 publications

(10 citation statements)

References 39 publications

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“…Gao et al (2021) found that SLC2A3 was correlated with EMT and immune signature in colorectal cancer. Fan et al (2022) verified that SLC25A38 was a In conclusion, this study first identifies the prognostic value of FLVCR2 in patients with AML. FLVCR2 expression is associated with immunocyte infiltration, such as NK cells, T cells, or macrophages in AML.…”

Section: Discussionsupporting

confidence: 60%

“… Gao et al (2021) found that SLC2A3 was correlated with EMT and immune signature in colorectal cancer. Fan et al (2022) verified that SLC25A38 was a novel biomarker for metastasis and clinical outcome in uveal melanoma. Our study focused on identifying FLVCR2 as a novel biomarker for AML, which may be an independent prognostic factor that influenced tumorigenesis and tumor immunology in AML progression.…”

Section: Discussionmentioning

confidence: 67%

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The prognostic marker FLVCR2 associated with tumor progression and immune infiltration for acute myeloid leukemia

Ma²,

Bai³

et al. 2022

Front. Cell Dev. Biol.

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Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies in adults. The tumor microenvironment (TME) has a critical effect on AML occurrence, recurrence, and progression. The gene feline leukemia virus subgroup C cellular receptor family member 2 (FLVCR2) belongs to the major facilitator superfamily of transporter protein members, which is primarily involved in transporting small molecules. The potential role of FLVCR2 in the TME in AML has not been investigated. To clarify the expression and role of FLVCR2 in AML, we analyzed the Gene Expression Omnibus and The Cancer Genome Atlas databases and found that FLVCR2 mRNA expression significantly increased among patients with AML. Furthermore, based on an analysis of the Gene Expression Profiling Interactive Analysis database, FLVCR2 upregulation predicted dismal overall survival of patients with AML. Our validation analysis revealed the significant upregulation of FLVCR2 within the bone marrow of AML relative to healthy controls by western blotting and qPCR assays. Gene set enrichment analysis was conducted to explore FLVCR2’s related mechanism in AML. We found that high FLVCR2 expression was related to infiltration degrees of immune cells and immune scores among AML cases, indicating that FLVCR2 possibly had a crucial effect on AML progression through the immune response. Specifically, FLVCR2 upregulation was negatively related to the immune infiltration degrees of activated natural killer cells, activated memory CD4+ T cells, activated dendritic cells, and CD8+ T cells using CIBERSORT analysis. According to the in vitro research, FLVCR2 silencing suppressed AML cell growth and promoted their apoptosis. This study provides insights into FLVCR2’s effect on tumor immunity, indicating that it might serve as an independent prognostic biomarker and was related to immune infiltration within AML.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 67%

The prognostic marker FLVCR2 associated with tumor progression and immune infiltration for acute myeloid leukemia

Ma²,

Bai³

et al. 2022

Front. Cell Dev. Biol.

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“…RNF43, SLC25A38, and CALHM2 are listed among the most differential UM survival genes based on transcriptome data from 80 UM cases from the TCGA dataset (26). The downregulation of SLC25A38, located on chromosome 3, was associated with enhanced migration of UM cells and promoted metastasis in mice models (44).…”

Section: Discussionmentioning

confidence: 94%

Aberrant DNA methylation of uveal melanoma drivers as an excellent prognostic tool

Šoltýsová

Dvorska

Kajabova

et al. 2023

Preprint

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Background: Despite outstanding advances in understanding the genetic background of uveal melanoma (UM) development and prognosis, the role of DNA methylation reprogramming remains elusive. This study aims to clarify the extent of DNA methylation deregulation in the context of gene expression changes and its utility as a reliable prognostic biomarker. Methods: Transcriptomic and DNA methylation landscapes in 25 high- and low-risk UMs were interrogated by Agilent SurePrint G3 Human Gene Expression 8×60K v2 Microarray and Human Infinium Methylation EPIC Bead Chip array, respectively. DNA methylation and gene expression of the nine top discriminatory genes, selected by the integrative analysis, were validated by pyrosequencing and qPCR in 58 tissues. Results: Among 2,262 differentially expressed genes discovered in UM samples differing in metastatic risk, 60 were epigenetic regulators, mostly histone modifiers and chromatin remodelers. 44,398 CpGs were differentially methylated, 27,810 hypomethylated, and 16,588 hypermethylated in high-risk tumors, with Δβ values ranging between -0.78 and 0.79. By integrative analysis, 944 differentially expressed DNA methylation-regulated genes were revealed, 635 hypomethylated/upregulated, and 309 hypermethylated/downregulated. Aberrant DNA methylation in high-risk tumors was associated with the deregulation of key oncogenic pathways such as EGFR tyrosine kinase inhibitor resistance, focal adhesion, proteoglycans in cancer, PI3K-Akt signaling, or ECM-receptor interaction. Notably, DNA methylation values of nine genes, HTR2B, AHNAK2, CALHM2, SLC25A38, EDNRB, TLR1, RNF43, IL12RB2, and MEGF10, validated by pyrosequencing, demonstrated excellent risk group prediction accuracies (AUC ranging between 0.870 and 0.956). Moreover, CALHM2 hypomethylation and MEGF10, TLR1 hypermethylation, as well as two three-gene methylation signatures, Signature 1 combining AHNAK2, CALHM2, and IL12RB and Signature 2 AHNAK2, CALHM2, and SLC25A38genes, correlated with shorter overall survival (HR = 4.38, 95% CI 1.30-16.41, HR = 5.59, 95% CI 1.30-16.41; HR = 3.43, 95% CI 1.30-16.41, HR = 4.61, 95% CI 1.30-16.41 and HR = 4.95, 95% CI 1.39-17.58, respectively). Conclusions: Our results demonstrate a significant role of DNA methylation aberrancy in UM progression. The advantages of DNA as a biological material and excellent prediction accuracies of methylation markers open the perspective for their more extensive clinical use.

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“…RNF43, SLC25A38, and CALHM2 are listed among the most differentially expressed UM survival genes based on transcriptome data from 80 UM cases from the TCGA dataset (26). The downregulation of SLC25A38, located on chromosome 3, was associated with enhanced migration of UM cells and promoted metastasis in mouse models (44). SLC25A38 is a mitochondrial glycine transporter that induces caspasedependent apoptosis.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation aberrancy is a reliable prognostic tool in uveal melanoma

Šoltýsová

Dvorska

Kajabova

et al. 2023

Preprint

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Background: Despite outstanding advances in understanding the genetic background of uveal melanoma (UM) development and prognosis, the role of DNA methylation reprogramming remains elusive. This study aims to clarify the extent of DNA methylation deregulation in the context of gene expression changes and its utility as a reliable prognostic biomarker. Methods: Transcriptomic and DNA methylation landscapes in 25 high- and low-risk UMs were interrogated by Agilent SurePrint G3 Human Gene Expression 8×60K v2 Microarray and Human Infinium Methylation EPIC Bead Chip array, respectively. DNA methylation and gene expression of the nine top discriminatory genes, selected by the integrative analysis, were validated by pyrosequencing and qPCR in 58 tissues. Results: Among 2,262 differentially expressed genes discovered in UM samples differing in metastatic risk, 60 were epigenetic regulators, mostly histone modifiers and chromatin remodelers. A total of 44,398 CpGs were differentially methylated, 27,810 hypomethylated, and 16,588 hypermethylated in high-risk tumors, with Δβ values ranging between -0.78 and 0.79. By integrative analysis, 944 differentially expressed DNA methylation-regulated genes were revealed, 635 hypomethylated/upregulated, and 309 hypermethylated/downregulated. Aberrant DNA methylation in high-risk tumors was associated with the deregulation of key oncogenic pathways such as EGFR tyrosine kinase inhibitor resistance, focal adhesion, proteoglycans in cancer, PI3K-Akt signaling, or ECM-receptor interaction. Notably, the DNA methylation values of nine genes, HTR2B, AHNAK2, CALHM2, SLC25A38, EDNRB, TLR1, RNF43, IL12RB2, and MEGF10, validated by pyrosequencing, demonstrated excellent risk group prediction accuracies (AUCs ranging between 0.870 and 0.956). Moreover, CALHM2 hypomethylation and MEGF10, TLR1 hypermethylation, as well as two three-gene methylation signatures, Signature 1 combining AHNAK2, CALHM2, and IL12RB and Signature 2 AHNAK2, CALHM2, and SLC25A38 genes, correlated with shorter overall survival (HR = 4.38, 95% CI 1.30-16.41, HR = 5.59, 95% CI 1.30-16.41; HR = 3.43, 95% CI 1.30-16.41, HR = 4.61, 95% CI 1.30-16.41 and HR = 4.95, 95% CI 1.39-17.58, respectively). Conclusions: Our results demonstrate a significant role of DNA methylation aberrancy in UM progression. The advantages of DNA as a biological material and the excellent prediction accuracies of methylation markers open the perspective for their more extensive clinical use.

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SLC25A38 as a novel biomarker for metastasis and clinical outcome in uveal melanoma

Cited by 9 publications

References 39 publications

The prognostic marker FLVCR2 associated with tumor progression and immune infiltration for acute myeloid leukemia

The prognostic marker FLVCR2 associated with tumor progression and immune infiltration for acute myeloid leukemia

Aberrant DNA methylation of uveal melanoma drivers as an excellent prognostic tool

DNA methylation aberrancy is a reliable prognostic tool in uveal melanoma

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