Exosomal IGFALS as a prognostic biomarker in hepatocellular Carcinoma: Associations with immune infiltration and clinical outcomes

IF 3.2 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes Pub Date : 2026-04-01 Epub Date: 2026-01-23 DOI:10.1016/j.mcp.2026.102061

Longfei Fan , Zhaoying Wang , Tao Tao , Dongdong Huang , Xiaoyun Tang , Rui Wang , Zhongqiang Qin , Bo Xie , Yi Tan

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引用次数: 0

Abstract

Purpose

This investigation seeks to examine the relationship between exosomal Insulin-like Growth Factor Binding Protein Acid Labile Subunit (IGFALS) gene expression, immune infiltration, and clinical outcomes in individuals with hepatocellular carcinoma (HCC).

Method

Clinical data and IGFALS expression levels were obtained from the TCGA and GEO databases. Immunohistochemistry was performed to confirm IGFALS expression in both HCC and adjacent non-tumor tissues. To validate survival analyses, restricted cubic spline models were used to explore associations between overall survival (OS) and the expression of IGFALS in liver hepatocellular carcinoma (LIHC). Gene set enrichment analysis (GSEA) identified IGFALS-associated pathways, while Gene set enrichment analysis (ssGSEA) evaluated IGFALS-immune cell infiltration correlations. Functional characterization included proliferation, migration/invasion, molecular profiling, and apoptosis assays.

Result

Compared to normal tissues, IGFALS expression levels were notably decreased in tumor tissues. A notable link was detected between IGFALS expression and multiple clinical factors, including gender, weight, residual tumor, adjacent hepatic tissue inflammation, vascular invasion, AFP, BCLC, tumor size, multinodular, TACE, and satellite lesion in HCC. Reduced IGFALS expression in HCC was correlated with decreased OS. Moreover, the IGFALS level in malignant tumor cells post-immunotherapy was observed to be markedly higher than that in the pre-treatment phase. A strong association between IGFALS and immune infiltration levels was also established. At the same time, in vitro experiments also verified the function of the IGFALS gene.

Conclusion

The exosomal IGFALS gene holds potential as a prospective indicator for assessing the outcome of individuals with HCC.

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外泌体IGFALS作为肝细胞癌的预后生物标志物：与免疫浸润和临床结果的关系

目的：本研究旨在探讨肝细胞癌（HCC）患者外泌体胰岛素样生长因子结合蛋白酸不稳定亚基（IGFALS）基因表达、免疫浸润和临床结局之间的关系。方法：从TCGA和GEO数据库中获取临床资料和IGFALS表达水平。免疫组织化学证实IGFALS在HCC和邻近非肿瘤组织中的表达。为了验证生存分析，我们使用限制三次样条模型来探讨肝细胞癌（LIHC）中总生存期（OS）与IGFALS表达之间的关系。基因集富集分析（GSEA）鉴定了igfals相关途径，而基因集富集分析（ssGSEA）评估了igfals与免疫细胞浸润的相关性。功能表征包括增殖、迁移/侵袭、分子分析和凋亡分析。结果：与正常组织相比，IGFALS在肿瘤组织中的表达水平明显降低。在HCC中，IGFALS的表达与性别、体重、肿瘤残留、邻近肝组织炎症、血管浸润、AFP、BCLC、肿瘤大小、多结节、TACE、卫星病变等临床因素均有显著相关性。HCC中IGFALS表达降低与OS降低相关。此外，免疫治疗后恶性肿瘤细胞中的IGFALS水平明显高于治疗前。IGFALS与免疫浸润水平之间也存在密切联系。同时，体外实验也验证了IGFALS基因的功能。结论：外泌体IGFALS基因有潜力作为评估HCC患者预后的前瞻性指标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular and Cellular Probes 生物-生化研究方法

CiteScore

6.80

自引率

0.00%

发文量

审稿时长

16 days

期刊介绍： MCP - Advancing biology throughâ€“omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.