Wang Shuai, Zhao Xunping, Zhu Shuyuan, Xu Jiali, Luo Tao
Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Genet Test Mol Biomarkers. 2023 Oct;27(10):325-338. doi: 10.1089/gtmb.2023.0075. Epub 2023 Oct 20.
Colorectal cancer (CRC) is a common malignancy of the digestive system, but its specific mechanisms of occurrence and development remain incompletely understood. F-Box and leucine-rich repeat protein 7 (FBXL7) is a subunit of the Skp-cullin-F-box ubiquitin ligase, involved in cell cycle regulation, endothelial cell damage, and inflammatory immunological responses. However, the role of FBXL7 in CRC remains unknown. In this study, we investigated the clinical significance and potential mechanism of FBXL7 expression in CRC progression. We utilized data from The Cancer Genome Atlas (TCGA) and the University of California Santa Cruz Xena (UCSC Xena) database for bioinformatic analyses. Clinical CRC samples were used to confirm FBXL7 expression. Gene set enrichment analysis (GSEA) and various databases, such as TCGA, UCSC Xena, cBioPortal, University of ALabama at Birmingham CANcer data analysis portal, MethSurv, Tumor Immune Estimation Resource (TIMER), TIMER2.0, Tumor-Immune System Interaction Database, and Tumor Immune Dysfunction and Exclusion Database (TIDB), were used to investigate the role of FBXL7 in CRC. Statistical analysis was performed using R (v.3.6.3) or GraphPad Prism 8.0. Our findings revealed the predictive significance of FBXL7 in CRC patients. FBXL7 expression was associated with tumor stage, lymph node stage, pathological stage, perineural invasion, and lymphatic invasion. GSEA analysis identified associations between FBXL7 and extracellular matrix organization, as well as immune-related pathways. Immunological analysis revealed a correlation between high FBXL7 expression and the development of an immunosuppressive microenvironment. Identifying FBXL7 as a novel biomarker for CRC could shed light on the promotion of CRC development by the immune environment.
结直肠癌（CRC）是消化系统常见的恶性肿瘤，但其发生和发展的具体机制仍未完全明确。F-Box和富含亮氨酸重复序列蛋白7（FBXL7）是Skp-泛素连接酶-Cullin-F-Box泛素连接酶的一个亚基，参与细胞周期调控、内皮细胞损伤及炎症免疫反应。然而，FBXL7在结直肠癌中的作用尚不清楚。在本研究中，我们探讨了FBXL7表达在结直肠癌进展中的临床意义及潜在机制。我们利用来自癌症基因组图谱（TCGA）和加利福尼亚大学圣克鲁兹分校Xena（UCSC Xena）数据库的数据进行生物信息学分析。采用临床结直肠癌样本确认FBXL7表达。利用基因集富集分析（GSEA）以及各种数据库，如TCGA、UCSC Xena、cBioPortal、阿拉巴马大学伯明翰分校癌症数据分析门户、MethSurv、肿瘤免疫评估资源（TIMER）、TIMER2.0、肿瘤-免疫系统相互作用数据库和肿瘤免疫功能障碍与排除数据库（TIDB），来研究FBXL7在结直肠癌中的作用。使用R（v.3.6.3）或GraphPad Prism 8.0进行统计分析。我们的研究结果揭示了FBXL7对结直肠癌患者的预测意义。FBXL7表达与肿瘤分期、淋巴结分期、病理分期、神经周围浸润和淋巴管浸润相关。GSEA分析确定了FBXL7与细胞外基质组织以及免疫相关通路之间的关联。免疫分析显示FBXL高表达与免疫抑制微环境的形成相关。将FBXL7鉴定为结直肠癌的一种新型生物标志物，可能有助于揭示免疫环境对结直肠癌发展的促进作用。
