Diagnostic and functional value of Homer2 in gastric cancer

ZHANG Yu; LIU Fenglian; TU Jiancheng

doi:10.14188/j.1671-8852.2024.1019

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Diagnostic and functional value of Homer2 in gastric cancer

更新时间：2026-11-06

- Diagnostic and functional value of Homer2 in gastric cancer
- Medical Journal of Wuhan University Vol. 46, Issue 12, Pages: 1559-1571(2025)
- 作者机构：
  
  武汉大学中南医院检验科湖北武汉 430071
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.1019
  CLC： R735.2
- Received：25 December 2024，
  
  Published：25 December 2025
- 稿件说明：
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张钰,刘凤莲,涂建成.Homer2在胃癌中的诊断价值及功能研究[J].武汉大学学报（医学版）,2025,46(12):1559-1571.

ZHANG Yu,LIU Fenglian,TU Jiancheng.Diagnostic and functional value of Homer2 in gastric cancer[J].Medical Journal of Wuhan University,2025,46(12):1559-1571.
张钰,刘凤莲,涂建成.Homer2在胃癌中的诊断价值及功能研究[J].武汉大学学报（医学版）,2025,46(12):1559-1571. DOI： 10.14188/j.1671-8852.2024.1019.

ZHANG Yu,LIU Fenglian,TU Jiancheng.Diagnostic and functional value of Homer2 in gastric cancer[J].Medical Journal of Wuhan University,2025,46(12):1559-1571. DOI： 10.14188/j.1671-8852.2024.1019.

摘要

目的

分析Homer2基因在胃癌（GC）中的表达水平，评估其在GC中的诊断和预后价值，探究其在GC发生发展中的作用，并分析其与GC肿瘤免疫浸润水平的相关性，预测其是否可作为GC的免疫治疗靶点。

方法

（1）通过癌症基因组图谱（TCGA）和人类蛋白质图谱（HPA）数据库获取Homer2在GC中的表达数据；（2）结合临床信息探究Homer2表达水平与临床特征相关性，采用受试者工作特征（ROC）曲线评估其诊断价值；（3）通过GO和KEGG功能富集分析预测Homer2的潜在功能；（4）通过CellMarker和TISIDB数据库分析Homer2与GC肿瘤免疫浸润水平相关性；（4）收集GC患者外周血及临床组织样本，检测Homer2的mRNA表达水平对生物信息学分析结果加以验证；（5）检测常见GC细胞系中Homer2的mRNA和蛋白质表达水平并进行细胞功能学实验；（6）通过OE‑Homer2慢病毒感染NCI‑N87和AGS细胞过表达Homer2，通过CCK‑8细胞增殖实验、克隆形成实验、细胞划痕实验和Transwell侵袭实验观察NCI‑N87和AGS细胞的增殖、迁移和侵袭能力的变化。

结果

（1）Homer2在GC组织中表达下调，其表达水平与病理分期、组织学分级、原发肿瘤大小分期和淋巴结转移分期水平呈负相关；（2）基于Homer2表达水平的ROC曲线的曲线下面积（

AUC

）为0.76（95%

：0.691~0.829）；（3）Homer2参与Wnt信号通路、参与单原子离子通道络合物且能影响DNA结合转录因子活性及RNA聚合酶Ⅱ的特异性，且与肌动蛋白细胞骨架的调节、MAPK、钙离子、Wnt以及mTOR信号通路的调节有相关性；（4）Homer2表达水平与GC肿瘤免疫浸润水平有一定相关性；（5）Homer2在GC患者外周血及组织中低表达，过表达Homer2后NCI‑N87和AGS细胞系的体外增殖、迁移和侵袭能力降低。以上结果差异均有统计学意义（

0.05）。

结论

Homer2在GC中表达下调；Homer2低表达与GC不良预后相关；Homer2可作为GC的诊断标志物和潜在的免疫治疗靶点。

Abstract

Objective

o analyze the expression level of the Homer2 gene in gastric cancer (GC)

to evaluate its diagnostic and prognostic value

to explore its role in GC development

to analyze its correlation with tumor immune⁃infiltration levels

and to assess its potential as an immunotherapy target for GC.

Methods

Homer2 expression data in GC were obtained from The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases

and clinical information was combined to investigate the correlation between Homer2 expression levels and clinical characteristics. The diagnostic value of Homer2 was evaluated using the receiver operating characteristic (ROC) curve. The function of Homer2 was predicted through GO and KEGG functional enrichment analysis. The correlation between Homer2 and tumor immune infiltration level was evaluated using CellMarker 2.0

an integrated repository portal for tumor‑immune system interactions (TISIDB) databases. Peripheral blood samples and tumor and non‑tumor samples of GC patients were collected to detect the mRNA expression level of Homer2. Moreover

the mRNA and protein expression levels of Homer2 were detected in common GC cell lines. Homer2 expression was reduced in GC cells via lentivirus infection. Cellular assays

including CCK⁃8 proliferation

clone formation

cell scratch

and Transwell invasion assays

were conducted to observe changes in cell proliferation

migration

and invasion abilities.

Results

The bioinformatics analysis showed that Homer2 expression was downregulated in GC tissues and negatively correlated with pathological staging

histological grading

primary tumor size

and lymph node metastasis. The

AUC

value of the ROC curve was 0.76 (95%

: 0.691⁃0.829). Homer2 was involved in the Wnt signaling pathway and ion channel complexes. It can also affect the activity of DNA⁃binding transcription factors and RNA polymerase Ⅱ. Furthermore

Homer2 was related to the regulation of the actin cytoskeleton

MAPK

calcium ion

Wnt

and mTOR signaling pathways. The expression level of Homer2 was correlated with the immune infiltration level in GC tumors. Homer2 was found to be downregulated in the perip

heral blood and tissue samples of patients with GC. Overexpression of Homer2 reduced the

in vitro

proliferation

migration

and invasion of GC cells (

0.05).

Conclusion

The expression of Homer2 was downregulated in GC

and low expression of Homer2 was associated with poor prognosis. Homer2 can be used as a diagnostic marker and a potential target for immunotherapy in GC.

关键词

Keywords

references

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