作者：申瑜峥1，严黛君1，常帅1，赵轶峰2

单位：1. 河北北方学院研究生院，河北 张家口 075000

2. 河北北方学院附属第一医院胃肠肿瘤外科，河北 张家口 075000

Authors: Shen Yuzheng1, Yan Daijun1, Chang Shuai1, Zhao Yifeng2

Unit：1.Graduate College, Hebei North University, Zhangjiakou 075000, Hebei, China；2.Department of Gastrointestinal Tumor Surgery, the First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, Hebei, China

摘要：

目的 分析成纤维细胞活化蛋白(fibroblast activation protein, FAP)基因在结肠癌中的表达情况，并探究其表达与结肠癌患者预后的相关性及潜在机制，为结肠癌的发病机制、诊断、治疗及预后提供新思路。方法 下载基因表达综合数据库和癌症基因组图谱数据库中结肠癌组织样本和癌旁正常组织样本的表达数据，分析FAP基因在结肠癌组织样本和癌旁正常组织样本中的表达情况。对Kaplan-Meier plotter数据库中结肠癌患者的生存资料进行生存分析，探究FAP基因表达与患者总生存率的相关性。使用GEPIA2数据库分析FAP基因在结肠癌患者中的表达及其对预后的作用。下载基因表达综合数据库和癌症基因组图谱数据库中结肠癌的临床相关数据，分析FAP基因在不同临床分期中的表达情况。通过基因集富集分析探索FAP基因与结肠癌发生、发展相关的分子作用通路。免疫相关性分析（CIBERSORT）用于探索FAP基因与免疫细胞浸润、免疫检查点表达的相关性。结果 FAP基因在结肠癌组织中的表达较癌旁正常组织上调（P﹤0.05）。结肠癌患者中FAP基因的表达水平在不同分期之间存在差异（P﹤0.05）。生存分析结果显示，高表达FAP基因患者的总生存率低于低表达FAP基因患者（P﹤0.05）。FAP基因通过多种通路影响结肠癌的发生发展。在结肠癌中，FAP基因与CD4⁺记忆T 细胞、浆细胞的浸润水平呈负相关，与常见免疫检查点表达呈正相关。结论 FAP基因在结肠癌中高表达，与患者不良预后显著相关。此外，FAP基因可通过多种细胞功能、化学通路以及免疫浸润等方式促进肿瘤的进展，是治疗结肠癌的潜在靶点。 

关键词： 成纤维细胞活化蛋白；结肠癌；标志物；生物信息

Abstract：

Objective  The objective of this study is to investigate the expression pattern of the fibroblast activation protein (FAP) gene in colon cancer and assess its association with patients’ clinical characteristics and prognosis, aiming to provide novel insights into the pathogenesis, diagnosis, treatment, and prognosis of colon cancer. Method  The RNA sequencing data of colon cancer tissues and adjacent normal tissues were downloaded from the gene expression omnibus database and the cancer gene atlas database. The expression level of FAP gene in adjacent normal tissues and colon cancer tissues was analyzed. Survival analysis was performed using colon cancer patients’ survival data from Kaplan-Meier plotter database to examine the relationship between FAP gene expression and overall survival rate. Furthermore, GEPIA2 database was utilized to assess FAP gene expression in colon cancer and its prognostic predictive effect. The clinical data of colon cancer were downloaded from the gene expression omnibus database and the cancer gene atlas database to explore the expression pattern of FAP gene in different stages. To investigate molecular pathways associated with the occurrence and development of colon cancer related to FAP gene, gene enrichment analysis was conducted. Immuno-correlation analysis (CIBERSORT) was employed to explore the association between FAP gene and immune cell infiltration and immune checkpoint expression. Result  Compared to adjacent normal tissues, the expression of FAP gene was upregulated in colon cancer tissues(P﹤0.05). The expression level of FAP gene was different among different stages in colon cancer patients(P﹤0.05). Survival analysis results demonstrated that patients with high FAP gene expression had a lower overall survival rate than those with low FAP gene expression (P﹤0.05). Furthermore, FAP gene influences the occurrence and progression of colon cancer through various pathways. In colon cancer specifically, FAP gene had a negative correlation with the infiltration levels of CD4⁺ memory T cells and plasma cells, and a positive correlation with the expression levels of common immune checkpoints. Conclusion  The expression of FAP gene is upregulated in colon cancer and is strongly associated with unfavorable survival outcomes and prognosis. FAP gene plays a crucial role in promoting tumor progression through diverse cellular functions, chemical pathways, and immune infiltration, thereby establishing itself as a promising therapeutic target for the treatment of colon cancer.

Key Words:  Fibroblast activating protein; Colon cancer; Biomarker; Bioinformation

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