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

• Published in: International immunopharmacology Vol. 147; p. 113841
• Main Authors: Weiqin, Liu, Qi, Wan, Lin, Jin, Shuxia, Chen, Chang, Liu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 06.02.2025
• Subjects: ACTL6A; Bioinformatics; Biomarkers, Tumor - genetics; Bulk RNA sequencing; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Immune infiltration; Immunotherapy; Melanoma - genetics; Melanoma - immunology; Melanoma - mortality; Melanoma - pathology; Neoplastic Stem Cells - immunology; Prognosis; Single-cell RNA sequencing; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Uveal Melanoma; Uveal Neoplasms - genetics; Uveal Neoplasms - immunology; Uveal Neoplasms - mortality; Uveal Neoplasms - pathology; GEPIA; IHC; Bulk RNA sequencing; H&E; Immune infiltration; ACTL6A; TIMER; Uveal melanoma; PPI; KNN; TCGA; GEO; Single-cell RNA sequencing; Immunotherapy; UM; Bioinformatics
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.113841

•Low expression of ACTL6A predicts poor prognosis of UM, closely related to metastasis, CSCs and immune infiltration.•IL13, TPTE, IL17B and CCL22 genes are significantly overexpressed, which is closely related to UM metastasis.•The metastasis of UM is mainly associated with CD4 Tconv, B , CD8 Tex, and Plasma. To predict and evaluate the possible mechanisms and clinical value of ACTL6A in the prognosis and development of UM. 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. 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. Downregulated ACTL6A acts as a risk factor for poor prognosis in UM, which implies as an potential prognostic marker for independent targeted immunotherapy.