揭示ACTL6A在葡萄膜黑色素瘤转移和免疫微环境中的作用。

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-02-06 DOI:10.1016/j.intimp.2024.113841

Liu Weiqin , Wan Qi , Jin Lin , Chen Shuxia , Liu Chang

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引用次数: 0

摘要

目的：预测和评价ACTL6A在UM预后发展中的可能机制及临床价值。方法：生物信息学分析ACTL6A与UM免疫的关系，数据来源于TCGA、Gene Expression Omnibus （GEO）数据库。使用QUANTISEQ和mcp计数器显示肿瘤膨胀的免疫细胞。利用scRNA-seq检测ACTL6A的表达、分布、免疫浸润，揭示UM的基因表达谱。结果：ACTL6A在UM中的表达低于TCGA数据库中的pantuma表达。Kaplan-Meier分析显示，下调的ACTL6A与不良OS相关，ACTL6A与肿瘤干细胞（CSCs）和免疫浸润相关。此外，ACTL6A可能作为化疗耐药基因，与上皮-间质转化密切相关。8个GSE数据库的分析显示，IL13、TPTE、IL17B和CCL22基因在转移性UM中显著过表达。此外，单细胞转录组学分析发现了一种新的细胞簇-作为一种独特的免疫细胞类型，它与恶性细胞的异质性和复杂性有关，并进一步揭示了UM的转移主要与CD4 Tconv， B， CD8 Tex和浆细胞有关。结论：ACTL6A下调是UM预后不良的危险因素，可能是独立靶向免疫治疗的潜在预后指标。

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Unveiling the role of ACTL6A in uveal melanoma metastasis and immune microenvironment

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.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

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.