Abstract

Background

ANXA1 is a calcium-dependent phospholipid-binding protein and is frequently associated with inflammation, cell proliferation and apoptosis. However, the relationship between ANXA1 and the prognosis of multiple tumours and tumour infiltrating immune cells remains unclear.

Methods

Multivariate Cox proportional regression analysis was used for signature genes exploration in the basic of colon adenocarcinoma (COAD) RNA-sequence dataset obtained from TCGA, following the identification of 267 common differentially expressed genes, including ANXA1, among three expression profile datasets (GSE41328, GSE110224, and GSE113513). The differential expression of ANXA1 in different tumours and their corresponding normal tissues were evaluated through the Tumour Immune Estimation Resource (TIMER) and Oncomine database. Subsequently, we investigated the correlation between the expression level of ANXA1 and diverse panel of infiltrating immune cells and their related gene markers in colorectal cancer using correlation analysis in TIMER and GEPIA database.

Results

The high expression of ANXA1 was demonstrated to be closely correlated with poor survival in patients with colorectal cancer. More importantly, we found that changes in ANXA1 expression showed a moderate to strong, and statistically significant, correlation with infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells. By contrast, there are only weak correlations between ANXA1 expression and immune cell infiltration in ESCA and STAD. ANXA1 expression was considerably associated with various immune markers involving immune cell recruitment, polarization of tumour-associated macrophages, and T cell exhaustion.

Conclusion

ANXA1 is not only an independent risk factor in the prediction of the prognosis of colorectal cancer, but also a crucial regulator in immune cell infiltration. This study may shed light on the clinical value of ANXA1, especially in the areas of early diagnosis of colorectal cancer and therapeutic target discovery.

中文翻译：

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鉴定 ANXA1 作为潜在的预后生物标志物并与结直肠癌中的免疫浸润相关联

摘要

背景

ANXA1 是一种钙依赖性磷脂结合蛋白，经常与炎症、细胞增殖和细胞凋亡有关。然而，ANXA1与多种肿瘤和肿瘤浸润免疫细胞的预后之间的关系尚不清楚。

方法

在从 TCGA 获得的结肠腺癌 (COAD) RNA 序列数据集中，在三个表达谱数据集 (GSE41328、GSE110224) 中鉴定出包括 ANXA1 在内的 267 个常见差异表达基因后，采用多元 Cox 比例回归分析进行特征基因探索，和 GSE113513）。通过肿瘤免疫估计资源（TIMER）和Oncomine数据库评估ANXA1在不同肿瘤及其相应正常组织中的差异表达。随后，我们使用 TIMER 和 GEPIA 数据库中的相关性分析研究了 ANXA1 的表达水平与多种浸润性免疫细胞及其相关基因标志物在结直肠癌中的相关性。

结果

ANXA1 的高表达被证明与结直肠癌患者的不良生存密切相关。更重要的是，我们发现 ANXA1 表达的变化与 B 细胞、CD8+ T 细胞、CD4+ T 细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润水平呈中到强且具有统计学意义的相关性。相比之下，在 ESCA 和 STAD 中，ANXA1 表达与免疫细胞浸润之间只有微弱的相关性。ANXA1 表达与各种免疫标志物密切相关，包括免疫细胞募集、肿瘤相关巨噬细胞的极化和 T 细胞耗竭。

结论

ANXA1不仅是预测结直肠癌预后的独立危险因素，也是免疫细胞浸润的重要调节因子。这项研究可能会阐明 ANXA1 的临床价值，尤其是在结直肠癌的早期诊断和治疗靶点发现领域。