Liu Weiqin , Wan Qi , Jin Lin , Chen Shuxia , Liu Chang
{"title":"Unveiling the role of ACTL6A in uveal melanoma metastasis and immune microenvironment","authors":"Liu Weiqin , Wan Qi , Jin Lin , Chen Shuxia , Liu Chang","doi":"10.1016/j.intimp.2024.113841","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>To predict and evaluate the possible mechanisms and clinical value of <em>ACTL6A</em> in the prognosis and development of UM.</div></div><div><h3>Methods</h3><div>Bioinformatics analyze the relationship between <em>ACTL6A</em> and immunity in UM, which derived from TCGA, Gene Expression Omnibus (GEO) databases. Tumor-infltrated immune cells were demonstrated using QUANTISEQ and MCP-counter. Furthermore, scRNA-seq was used to detect <em>ACTL6A</em> expression, distribution, immune infiltration and revealing the gene expression profile of UM.</div></div><div><h3>Results</h3><div>The expression of <em>ACTL6A</em> was lower in UM compared with pantumor in TCGA databases. Kaplan-Meier analysis revealed that downregulated <em>ACTL6A</em> was associated with poor OS, and <em>ACTL6A</em> was associated with cancer stem cells (CSCs) and immune infiltration. Moreover, <em>ACTL6A</em> might act as a chemotherapy resistance gene and closely relate- to epithelial-mesenchymal transition. Analysis in 8 GSE databases showed that <em>IL13, TPTE, IL17B</em> and <em>CCL22</em> genes were significantly overexpressed in metastatic UM. Furthermore, the single-cell transcriptomic profling identified a new cell cluster - as a unique type of immune cell, which associating with malignant cell heterogeneity and complexity, and further revealing that the metastasis of UM is mainly associated with CD4 Tconv, B , CD8 Tex, and Plasma cells.</div></div><div><h3>Conclusions</h3><div>Downregulated ACTL6A acts as a risk factor for poor prognosis in UM, which implies as an potential prognostic marker for independent targeted immunotherapy.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"147 ","pages":"Article 113841"},"PeriodicalIF":4.8000,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576924023634","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose
To predict and evaluate the possible mechanisms and clinical value of ACTL6A in the prognosis and development of UM.
Methods
Bioinformatics analyze the relationship between ACTL6A and immunity in UM, which derived from TCGA, Gene Expression Omnibus (GEO) databases. Tumor-infltrated immune cells were demonstrated using QUANTISEQ and MCP-counter. Furthermore, scRNA-seq was used to detect ACTL6A expression, distribution, immune infiltration and revealing the gene expression profile of UM.
Results
The expression of ACTL6A was lower in UM compared with pantumor in TCGA databases. Kaplan-Meier analysis revealed that downregulated ACTL6A was associated with poor OS, and ACTL6A was associated with cancer stem cells (CSCs) and immune infiltration. Moreover, ACTL6A might act as a chemotherapy resistance gene and closely relate- to epithelial-mesenchymal transition. Analysis in 8 GSE databases showed that IL13, TPTE, IL17B and CCL22 genes were significantly overexpressed in metastatic UM. Furthermore, the single-cell transcriptomic profling identified a new cell cluster - as a unique type of immune cell, which associating with malignant cell heterogeneity and complexity, and further revealing that the metastasis of UM is mainly associated with CD4 Tconv, B , CD8 Tex, and Plasma cells.
Conclusions
Downregulated ACTL6A acts as a risk factor for poor prognosis in UM, which implies as an potential prognostic marker for independent targeted immunotherapy.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.