Expression of the Vesicular Monoamine Transporter Gene Solute Carrier Family 18 Member 1 (<i>SLC18A1</i>) in Lung Cancer

Lehrer, Steven; Rheinstein, Peter H.

doi:10.21873/cgp.20097

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…Specifically, the high expression of the MEIS family is associated with the upregulation of C5. Previous studies by Lehrer et al have reported that high levels of C5 (immune silencing) will weaken the efficacy of immune checkpoint inhibitors (27). It is suggested that for patients with advanced cancer, interfering with the expression of MEIS while using immune checkpoint inhibitors may benefit the patients.…”

Section: Discussionmentioning

confidence: 99%

Effect of myeloid ecotropic viral integration site (MEIS) family genes on tumor microenvironment remodeling and its potential therapeutic effect

Meng¹,

Tian²,

Wang³

et al. 2021

Transl Androl Urol

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Background: The myeloid ecotropic viral integration site (MEIS) family of genes is related to the occurrence, development, and outcome of many cancers. However, its role in the immune and tumor microenvironment (TME) is unclear. This study explored the relationship between the expression of MEIS genes and patient survival, immune subtypes, TME, tumor stem cell correlation, and drug sensitivity in cancer. Methods: We used The Cancer Genome Atlas pan-cancer data to analyze the expression of the MEIS family genes. Kaplan-Meier analysis and univariate Cox proportional hazard regression model were used to detect the relationship between gene expression and overall survival. Analysis of variance was used to explore the relationship between the MEIS family and the immune components in the tumor, and the ESTIMATE algorithm was used to calculate the proportion and level of tumor-infiltrating immune cells. Spearman and Pearson's correlation tests were carried out to detect the relationship between MEIS and the characteristics of tumor stem cells and drug sensitivity. Results: The MEIS family of genes shows different expression profiles in different cancers, with substantial inter-and intra-cancer heterogeneity. Among them, MEIS3 was upregulated in most cancers, whereas MEIS2 was downregulated. The change in MEIS gene expression was usually related to overall survival, but whether a member of the MEIS family was a risk factor or a protective factor was cancer-dependent. Immune component analysis suggested that the role of MEIS genes in promoting or inhibiting cancer may be related to different degrees of immune silencing. Further, there were varying degrees of correlation between MEIS gene expression and cancer cell stemness characteristics. It was also found that MEIS genes, especially MEIS1 and MEIS2, may be related to chemotherapy resistance. Conclusions: We explored the expression, prognostic relationship, molecular characteristics, and effects on immunity and TME of the MEIS gene family in cancer. Our results suggest that MEIS members should be studied as independent entities in different types of cancer. The MEIS gene family may be a potential target for cancer therapy, but further experiments are needed to confirm this.

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Section: Discussionmentioning

confidence: 99%

Effect of myeloid ecotropic viral integration site (MEIS) family genes on tumor microenvironment remodeling and its potential therapeutic effect

Meng¹,

Tian²,

Wang³

et al. 2021

Transl Androl Urol

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“…Among them, C5 is positively correlated to MEIS1. A high level of C5 can impair the curative effect of immune checkpoint inhibitors, as reported by Lehrer and his colleagues [ 42 ]. Our findings showed that MEIS1 expression was strongly related to most immune cells in various types of cancer.…”

Section: Discussionmentioning

confidence: 91%

A Systematic Pan-Cancer Analysis of MEIS1 in Human Tumors as Prognostic Biomarker and Immunotherapy Target

Han

Tang

Hua

et al. 2023

JCM

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Background: We intended to explore the potential immunological functions and prognostic value of Myeloid Ecotropic Viral Integration Site 1 (MEIS1) across 33 cancer types. Methods: The data were acquired from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene expression omnibus (GEO) datasets. Bioinformatics was used to excavate the potential mechanisms of MEIS1 across different cancers. Results: MEIS1 was downregulated in most tumors, and it was linked to the immune infiltration level of cancer patients. MEIS1 expression was different in various immune subtypes including C2 (IFN-gamma dominant), C5 (immunologically quiet), C3 (inflammatory), C4 (lymphocyte depleted), C6 (TGF-b dominant) and C1 (wound healing) in various cancers. MEIS1 expression was correlated with Macrophages_M2, CD8+T cells, Macrophages_M1, Macrophages_M0 and neutrophils in many cancers. MEIS1 expression was negatively related to tumor mutational burden (TMB), microsatellite instability (MSI) and neoantigen (NEO) in several cancers. Low MEIS1 expression predicts poor overall survival (OS) in adrenocortical carcinoma (ACC), head and neck squamous cell carcinoma (HNSC), and kidney renal clear cell carcinoma (KIRC) patients, while high MEIS1 expression predicts poor OS in colon adenocarcinoma (COAD) and low grade glioma (LGG) patients. Conclusion: Our findings revealed that MEIS1 is likely to be a potential new target for immuno-oncology.

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“…In cancer, dysregulation of SLC proteins has been shown to be oncogenic ( Xie et al, 2011 ; Mohelnikova-Duchonova et al, 2013 ; Bhutia et al, 2016 ; Sutherland et al, 2020 ). Many SLCs have been reported to be aberrantly expressed in LUAD and might serve as prognostic biomarkers ( Ikeda et al, 2015 ; Lehrer and Rheinstein, 2018 ). For example, elevated expression of SLC2A1 was associated with a poorer prognosis in LUAD patients ( Guo et al, 2020 ), while increased SLC18A1 expression was associated with significantly increased survival in LUAD patients ( Lehrer and Rheinstein, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Many SLCs have been reported to be aberrantly expressed in LUAD and might serve as prognostic biomarkers ( Ikeda et al, 2015 ; Lehrer and Rheinstein, 2018 ). For example, elevated expression of SLC2A1 was associated with a poorer prognosis in LUAD patients ( Guo et al, 2020 ), while increased SLC18A1 expression was associated with significantly increased survival in LUAD patients ( Lehrer and Rheinstein, 2018 ). Additionally, aberrant SLC expression contributes to accelerated cell proliferation and invasion through diverse mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma

Zhu

Mou

et al. 2021

Front. Cell Dev. Biol.

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Given the importance of solute carrier (SLC) proteins in maintaining cellular metabolic homeostasis and that their dysregulation contributes to cancer progression, here we constructed a robust SLC family signature for lung adenocarcinoma (LUAD) patient stratification. Transcriptomic profiles and relevant clinical information of LUAD patients were downloaded from the TCGA and GEO databases. SLC family genes differentially expressed between LUAD tissues and adjacent normal tissues were identified using limma in R. Of these, prognosis-related SLC family genes were further screened out and used to construct a novel SLC family-based signature in the training cohort. The accuracy of the prognostic signature was assessed in the testing cohort, the entire cohort, and the external GSE72094 cohort. Correlations between the prognostic signature and the tumor immune microenvironment and immune cell infiltrates were further explored. We found that seventy percent of SLC family genes (279/397) were differentially expressed between LUAC tissues and adjacent normal. Twenty-six genes with p-values < 0.05 in univariate Cox regression analysis and Kaplan-Meier survival analysis were regarded as prognosis-related SLC family genes, six of which were used to construct a prognostic signature for patient classification into high- and low-risk groups. Kaplan-Meier survival analysis in all internal and external cohorts revealed a better overall survival for patients in the low-risk group than those in the high-risk group. Univariate and multivariate Cox regression analyses indicated that the derived risk score was an independent prognostic factor for LUAD patients. Moreover, a nomogram based on the six-gene signature and clinicopathological factors was developed for clinical application. High-risk patients had lower stromal, immune, and ESTIMATE scores and higher tumor purities than those in the low-risk group. The proportions of infiltrating naive CD4 T cells, activated memory CD4 T cells, M0 macrophages, resting dendritic cells, resting mast cells, activated mast cells, and eosinophils were significantly different between the high- and low-risk prognostic groups. In all, the six-gene SLC family signature is of satisfactory accuracy and generalizability for predicting overall survival in patients with LUAD. Furthermore, this prognostics signature is related to tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.

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Expression of the Vesicular Monoamine Transporter Gene Solute Carrier Family 18 Member 1 (SLC18A1) in Lung Cancer

Cited by 6 publications

References 32 publications

Effect of myeloid ecotropic viral integration site (MEIS) family genes on tumor microenvironment remodeling and its potential therapeutic effect

Effect of myeloid ecotropic viral integration site (MEIS) family genes on tumor microenvironment remodeling and its potential therapeutic effect

A Systematic Pan-Cancer Analysis of MEIS1 in Human Tumors as Prognostic Biomarker and Immunotherapy Target

Identification of a Six-Gene SLC Family Signature With Prognostic Value in Patients With Lung Adenocarcinoma

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