COL5A2 是 COL5 家族的一个成员，其高表达预示着胃癌患者生存不良，并促进肿瘤细胞迁移。
High expression of COL5A2, a member of COL5 family, indicates the poor survival and facilitates cell migration in gastric cancer.
机构信息
Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Cell Biology, Key Laboratory of Cell Biology of Ministry of Public Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, China Medical University, No. 77, Puhe Road, Shenyang North New Area, 110122 Shenyang, Liaoning, China.
出版信息
Biosci Rep. 2021 Apr 30;41(4). doi: 10.1042/BSR20204293.
BACKGROUND
Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. The present study aimed to explore the expression profile and role of COL5A2, as an extracellular matrix protein, in GC.
METHODS
The expression, overall survival, and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas (TCGA) database, respectively. Weighted gene co-expression network analysis of the GSE62229 database was performed out to identify modules and associated genes.
RESULTS
COL5A2 was selected as our research target in the TCGA database, and was also verified in the GSE62229 and GSE15459 datasets. COL5A2 was up-regulated in GC tissues by paraffin immunohistochemistry and RT-qPCR. The prognosis of patients with low COL5A2 expression was better than that of patients with high COL5A2 expression. Scratch and migration experiments showed that knockdown of COL5A2 decreased the migration ability of gastric cancer cells compared with the control group. In vivo, mice with tail vein injection COL5A2 knockdown had fewer and smaller metastatic nodules in liver. GSEA results showed that the TCGA and GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways.
CONCLUSION
COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis, and may be a novel therapeutic target for GC.
背景
胃癌（GC）转移决定了患者的预后，探索 GC 转移的分子机制有望为临床治疗提供理论依据。最近的研究表明，细胞外基质蛋白与 GC 转移密切相关。本研究旨在探讨细胞外基质蛋白 COL5A2 在 GC 中的表达谱和作用。
方法
分别从癌症基因组图谱（TCGA）数据库中提取 COL5 家族成员的表达、总生存和无进展生存数据。对 GSE62229 数据库进行加权基因共表达网络分析，以识别模块和相关基因。
结果
在 TCGA 数据库中选择 COL5A2 作为我们的研究目标，并在 GSE62229 和 GSE15459 数据集进行验证。COL5A2 在 GC 组织中的表达通过石蜡免疫组化和 RT-qPCR 得到验证。低 COL5A2 表达患者的预后优于高 COL5A2 表达患者。划痕和迁移实验表明，与对照组相比，COL5A2 敲低降低了胃癌细胞的迁移能力。体内实验中，尾静脉注射 COL5A2 敲低的小鼠肝脏中转移结节数量更少、体积更小。GSEA 结果表明，TCGA 和 GSE62229 样本在几个已知的癌症相关途径中显著富集，如 TGF-β、MAPK 和 JAK2 信号通路。
结论
COL5A2 在 COL5 家族成员中与晚期 GC 最密切相关。COL5A2 高表达与预后不良相关，可能成为 GC 的一个新的治疗靶点。
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