Zhang H, Zhang Z, Wang Q, Wang L, Yang Z, Geng Z, Wang Y, Li J, Zuo L
Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2023 Jun 20;43(6):975-984. doi: 10.12122/j.issn.1673-4254.2023.06.13.
To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.
The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.
GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues ( < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients ( < 0.05) and served as an independent risk factor for poor survival outcomes in GC ( < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC ( < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation ( < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors ( < 0.05).
FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.
探讨四联体盒激酶1（FJX1）在胃癌（GC）中的表达情况，其与患者生存结局的相关性及其在胃癌进展中的作用。
利用TCGA和GEO数据库中的胃癌队列分析FJX1在胃癌组织和正常胃黏膜组织中的表达水平及其与胃癌患者生存结局的相关性。采用免疫组织化学法检测胃癌组织临床标本中FJX1的表达水平，并分析其与患者临床病理参数及预后的相关性。进行生物信息学分析以确定FJX1在胃癌中的潜在作用途径。使用CCK-8法和蛋白质印迹法评估FJX1过表达或FJX1沉默对胃癌细胞增殖及增殖相关蛋白PI3K、AKT、p-PI3K和p-AKT表达的影响。在裸鼠中评估FJX1过表达对胃癌细胞致瘤性的影响。
与正常胃黏膜组织相比，胃癌组织中FJX1 mRNA和蛋白表达显著更高（<0.05）。FJX1高表达与胃癌患者预后不良相关（<0.05），并是胃癌患者生存结局不良的独立危险因素（<0.05）。FJX1主要在胃癌细胞的细胞质中表达，与Ki67表达呈正相关（R=0.34，<0.05），并与胃癌的CA199水平、肿瘤浸润深度和淋巴结转移相关（<0.05）。在细胞实验中，FJX1水平显示可调节Ki67和PCNA的表达以及胃癌细胞增殖（<0.05）。基因集富集分析表明PI3K/AKT途径可能介导FJX1的作用，其调节PI3K和AKT及其磷酸化蛋白的表达。在裸鼠中，胃癌细胞中FJX1过表达显著促进移植瘤生长（<0.05）。
FJX1在胃癌组织中高表达，与胃癌患者预后不良相关。FJX1过表达通过PI3K/AKT信号通路促进胃癌细胞增殖，可能作为胃癌潜在的预后生物标志物和治疗靶点。
