ARL9 在结肠腺癌中上调，可作为预后不良的生物标志物。
ARL9 is upregulated and serves as a biomarker for a poor prognosis in colon adenocarcinoma.
机构信息
Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.
Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China.
出版信息
BMC Gastroenterol. 2023 Feb 23;23(1):48. doi: 10.1186/s12876-023-02677-8.
BACKGROUND
ARL9 is a newly identified member of the ARF family, and the clinical significance of ARL9 in colon adenocarcinoma is unknown. In this study, we aimed to explore the expression of ARL9 mRNA in colon adenocarcinoma, and its effect on the prognosis of patients with colon adenocarcinoma.
METHODS
We investigated the differential expression of ARL9 between colon adenocarcinoma tissue and adjacent tissues through a bioinformatics analysis using The Cancer Genome Atlas (TCGA) database. The correlation between clinical characteristics and the mRNA expression level of ARL9 were analyzed. A survival analysis and a Cox regression analysis were used to determine the prognostic significance of ARL9. Finally, we conducted a gene set enrichment analysis (GSEA) to explore the ARL9 signaling pathways involved in the development of colon adenocarcinoma. The effect of the expression of ARL9 on the proliferation and migration of colon adenocarcinoma was analyzed by the CCK8 method and a cell scratch test, respectively.
RESULTS
The mRNA expression of ARL9 in colon adenocarcinoma tissues was higher in comparison to the level in normal adjacent tissues (P < 0.05). The mRNA expression of ARL9 was not related to sex, tumor stage, T stage, N stage, M stage, but to age. The 5-year survival rate of colon adenocarcinoma patients with high ARL9 mRNA expression levels was significantly lower than that of patients with low ARL9 mRNA expression levels (P < 0.05). Age and the high mRNA expression of ARL9 were independent risk factors for a poor prognosis in patients with colon adenocarcinoma. The GSEA suggested that ARL9 may be able to upregulate cell adhesion, extracellular matrix receptor interactions, tumor-associated pathways, and downregulate the citrate cycle and tricarboxylic acid cycle pathway, which are involved in the development of colon adenocarcinoma. After knocking down ARL9, the proliferation and migration abilities of colon adenocarcinoma cells were decreased (P < 0.01).
CONCLUSION
The mRNA expression of ARL9 is upregulated in colon adenocarcinoma, and higher mRNA expression levels are associated with a poor prognosis. Knocking down ARL9 can reduce the proliferation and migration of colon adenocarcinoma cells. ARL9 mRNA can be used as a prognostic biomarker in patients with colon adenocarcinoma.
背景
ARL9 是 ARF 家族的新成员，其在结肠腺癌中的临床意义尚不清楚。本研究旨在探讨 ARL9mRNA 在结肠腺癌中的表达及其对结肠腺癌患者预后的影响。
方法
我们通过使用癌症基因组图谱（TCGA）数据库的生物信息学分析来研究 ARL9 在结肠腺癌组织与相邻组织之间的差异表达。分析了 ARL9mRNA 表达水平与临床特征之间的相关性。采用生存分析和 Cox 回归分析来确定 ARL9 的预后意义。最后，我们进行了基因集富集分析（GSEA），以探讨 ARL9 信号通路在结肠腺癌发生发展中的作用。通过 CCK8 法和细胞划痕试验分别分析 ARL9 表达对结肠腺癌增殖和迁移的影响。
结果
与正常相邻组织相比，结肠腺癌组织中 ARL9mRNA 的表达水平更高（P<0.05）。ARL9mRNA 的表达与性别、肿瘤分期、T 分期、N 分期、M 分期无关，但与年龄有关。ARL9mRNA 高表达的结肠腺癌患者的 5 年生存率明显低于 ARL9mRNA 低表达的患者（P<0.05）。年龄和 ARL9mRNA 高表达是结肠腺癌患者预后不良的独立危险因素。GSEA 提示 ARL9 可能上调细胞黏附、细胞外基质受体相互作用、肿瘤相关途径，下调柠檬酸循环和三羧酸循环途径，从而参与结肠腺癌的发生发展。敲低 ARL9 后，结肠腺癌细胞的增殖和迁移能力下降（P<0.01）。
结论
ARL9mRNA 在结肠腺癌中呈上调表达，且高表达水平与预后不良相关。敲低 ARL9 可降低结肠腺癌细胞的增殖和迁移能力。ARL9mRNA 可作为结肠腺癌患者的预后标志物。
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