Lu Xiao-Fei, Zhang Hong-Wei, Chang Xiao, Guo Yong-Ze
Department of Clinical Medicine, Hebei University of Engineering, Handan 056002, Hebei Province, China.
Department of Gastroenterology, Affiliated Hospital of Hebei Engineering University, Handan 056002, Hebei Province, China.
World J Gastrointest Oncol. 2025 Apr 15;17(4):102913. doi: 10.4251/wjgo.v17.i4.102913.
Colon cancer represents a significant malignant neoplasm within the digestive system, characterized by a high incidence rate and substantial disease burden. The F-box protein 22 (FBXO22) plays a role in forming a specific type of ubiquitin ligase subunit, which is expressed abnormally in various malignant neoplasms and shows a notable relationship with prognosis in patients with cancer. Nevertheless, the function of FBXO22 in the context of colon cancer remains inadequately elucidated.
To explore the role of FBXO22 in colon cancer by examining FBXO22 expression patterns and analyzing how the protein affects the prognosis in patients who have undergone surgery.
Samples of cancerous and nearby normal tissues from patients with colon cancer were gathered, along with pertinent clinical data. Expression levels of the gene in both cancerous and paracancerous tissues were assessed through immunohistochemistry. The median H score served as a criterion for categorizing gene expression into high and low levels in cancerous tissues, and the relationship between these expression levels and various pathologic characteristics of patients, such as age, sex, and clinical stage, was analyzed. Colon cancer cell lines HCT116 and DLD-1 were used and divided into three groups: A blank control group, a negative control group, and a si-FBXO22 group. FBXO22 gene mRNA and protein expression were measured 24 hours post-transfection using real-time fluorescence quantitative polymerase chain reaction and western blotting. The proliferation capabilities of the cells in each group were assessed using the Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine assay, while cellular migration and invasion abilities were evaluated using scratch healing and Transwell assays. Various online platforms, including the Timer Immune Estimation Resource, were used to analyze pan-cancer expression, promoter methylation levels, and mutation frequencies of the gene in colon cancer patients. Additionally, the correlation between gene expression, patient prognosis, immune cell infiltration, and the expression of immune molecules in the colon cancer microenvironment was investigated. The relationship between gene expression and chemotherapy resistance, along with the potential mechanisms of action of the gene, were analyzed using The Cancer Genome Atlas dataset and the Genomics of Drug Sensitivity in Cancer drug training set R software.
Compared with normal colonic tissues, the gene was highly expressed in colon cancer tissues. Post-operative patients with colon cancer elevated FBXO22 reduced survival and exhibited resistance to various chemotherapeutic agents. FBXO22 expression suppresses the infiltration of anti-tumor immune cells. , FBXO22 knockdown inhibited the proliferation and migration of colon cancer cells.
The gene is a biomarker of poor prognosis in patients with colon cancer and has potential as a target for immunotherapy and overcoming chemotherapy resistance.
结肠癌是消化系统中一种重要的恶性肿瘤，发病率高，疾病负担重。F-box蛋白22（FBXO22）在形成特定类型的泛素连接酶亚基中发挥作用，在各种恶性肿瘤中异常表达，与癌症患者的预后有显著关系。然而，FBXO22在结肠癌中的功能仍未得到充分阐明。
通过检测FBXO22的表达模式并分析该蛋白如何影响接受手术患者的预后，探讨FBXO22在结肠癌中的作用。
收集结肠癌患者的癌组织和癌旁正常组织样本以及相关临床资料。通过免疫组织化学评估该基因在癌组织和癌旁组织中的表达水平。中位H评分作为将癌组织中该基因表达分为高水平和低水平的标准，并分析这些表达水平与患者的各种病理特征（如年龄、性别和临床分期）之间的关系。使用结肠癌细胞系HCT116和DLD-1，并分为三组：空白对照组、阴性对照组和si-FBXO22组。转染后24小时，使用实时荧光定量聚合酶链反应和蛋白质印迹法测量FBXO22基因的mRNA和蛋白质表达。使用细胞计数试剂盒-8法和5-乙炔基-2'-脱氧尿苷法评估每组细胞的增殖能力，同时使用划痕愈合和Transwell法评估细胞迁移和侵袭能力。使用包括Timer免疫评估资源在内的各种在线平台分析结肠癌患者中该基因的泛癌表达、启动子甲基化水平和突变频率。此外，研究该基因表达与患者预后、免疫细胞浸润以及结肠癌微环境中免疫分子表达之间的相关性。使用癌症基因组图谱数据集和癌症药物敏感性基因组学药物训练集R软件分析该基因表达与化疗耐药性之间的关系以及该基因的潜在作用机制。
与正常结肠组织相比，该基因在结肠癌组织中高表达。结肠癌术后患者中FBXO22升高会降低生存率并表现出对各种化疗药物的耐药性。FBXO22表达抑制抗肿瘤免疫细胞的浸润。此外，敲低FBXO22可抑制结肠癌细胞的增殖和迁移。
该基因是结肠癌患者预后不良的生物标志物，具有作为免疫治疗靶点和克服化疗耐药性的潜力。
