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LRFN4的全癌综合分析：其作为免疫治疗预后生物标志物和治疗靶点的潜力。

A comprehensive pan-cancer analysis of LRFN4: its potential as a prognostic biomarker and therapeutic target for immunotherapy.

作者信息

Xu Yinmei, Wu Xin, Zhi Peng, Guo Genyu, Fu Yankan, You Lukuan, Huai Siyuan, Li Jianxiong

机构信息

Medical College, People's Liberation Army General Hospital, Beijing, China.

Department of General Surgery, People's Liberation Army General Hospital, Beijing, China.

出版信息

Front Immunol. 2025 May 2;16:1539076. doi: 10.3389/fimmu.2025.1539076. eCollection 2025.

DOI:10.3389/fimmu.2025.1539076
PMID:40386777
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12081452/
Abstract

BACKGROUND

LRFN4, characterized by leucine-rich repeats and fibronectin type III domains, has been implicated in various human diseases. However, its role in immune regulation and cancer prognosis remains unclear.

METHODS

We performed a comprehensive analysis using datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTE x), UALCAN, Star Base, and Comparative Toxicogenomics Database (CTD), and observed significant dysregulation of LRFN4 in multiple cancers compared to normal tissues.

RESULTS

LRFN4 expression was strongly correlated with clinical prognosis, immune subtypes, molecular subtypes, immune checkpoint (ICP) genes, tumor mutational burden (TMB), microsatellite instability (MSI), and immune infiltration, which were measured by ESTIMATE scores. Moreover, LRFN4 expression was associated with the presence of tumor-infiltrating immune cells, particularly in gastrointestinal tumors, reflecting immune cell genetic signatures. Validation through fluorescence multiplex immunohistochemistry confirmed that the association of LRFN4 protein expression with the clinicopathological features and the immune microenvironment of gastric cancer. Flow cytometry analysis indicated that LRFN4 inhibited apoptosis in gastric cancer cell lines while enhancing cell cycle arrest in the S phase. Western Blot analysis demonstrated a positive correlation between the high expression of LRFN4 and the expression levels of cyclin D1 as well as CDK4. In contrast, a negative correlation was observed between the high expression of LRFN4 and the expression level with cleaved-caspase-3 levels.

CONCLUSION

These findings suggest that LRFN4 may serve as a novel biomarker for cancer prognosis and a potential target for immunotherapy.

摘要

背景

富含亮氨酸重复序列和III型纤连蛋白结构域的LRFN4与多种人类疾病有关。然而，其在免疫调节和癌症预后中的作用仍不清楚。

方法

我们使用来自癌症基因组图谱（TCGA）、癌细胞系百科全书（CCLE）、基因型-组织表达项目（GTEx）、UALCAN、星基数据库（Star Base）和比较毒理基因组学数据库（CTD）的数据集进行了全面分析，发现与正常组织相比，LRFN4在多种癌症中存在明显的失调。

结果

LRFN4表达与临床预后、免疫亚型、分子亚型、免疫检查点（ICP）基因、肿瘤突变负担（TMB）、微卫星不稳定性（MSI）和免疫浸润密切相关，这些通过ESTIMATE评分来衡量。此外，LRFN4表达与肿瘤浸润免疫细胞的存在有关，特别是在胃肠道肿瘤中，反映了免疫细胞的遗传特征。通过荧光多重免疫组织化学验证，证实了LRFN4蛋白表达与胃癌的临床病理特征和免疫微环境之间的关联。流式细胞术分析表明，LRFN4抑制胃癌细胞系的凋亡，同时增强S期的细胞周期阻滞。蛋白质免疫印迹分析表明，LRFN4的高表达与细胞周期蛋白D1以及细胞周期蛋白依赖性激酶4的表达水平呈正相关。相反，观察到LRFN4的高表达与裂解的半胱天冬酶-3水平呈负相关。

结论

这些发现表明，LRFN4可能作为一种新的癌症预后生物标志物和免疫治疗的潜在靶点。

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