Xie Tianyu, Guo Xin, Wu Di, Li Shuo, Lu Yixun, Wang Xinxin, Chen Lin
School of Medicine, Nankai University, Tianjin, China.
Department of General Surgery, Chinese PLA General Hospital, Beijing, China.
Front Oncol. 2021 Feb 25;11:591545. doi: 10.3389/fonc.2021.591545. eCollection 2021.
Platelet activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3) is associated with a variety of human diseases. However, its function in gastric cancer remains uncertain.
PAFAH1B3 expression was analyzed in The Cancer Genome Atlas (TCGA) and genotype-tissue expression pan-cancer data. The association between PAFAH1B3 expression and patient prognosis was evaluated using TCGA clinical survival data. Enrichment analysis of PAFAH1B3 was performed using the R software package. Moreover, the correlation between PAFAH1B3 expression and immune cell infiltration were evaluated by analyzing TCGA database. CCK8 assay and colony-formation assay were performed to assess the effect of PAFAH1B3 on the proliferation of gastric cancer cells. Transwell assay was used to evaluate the impact of PAFAH1B3 on gastric cancer cell migration. Western blot was performed to evaluate the role of PAFAH1B3 on signaling pathways in gastric cancer cells.
PAFAH1B3 was highly expressed in many types of tumors including gastric cancer. High PAFAH1B3 expression was significantly correlated with proliferation-related gene sets involved in DNA replication, the cell cycle, and cell cycle checkpoints. Further analysis showed that high PAFAH1B3 expression was associated with high M1 macrophage and CD8-positive T cell infiltration scores. PAFAH1B3 knockdown inhibited the proliferation, migration, and the activation of oncogenic signaling in gastric cancer cells.
Our findings suggest that PAFAH1B3 may be an oncogene in gastric cancer.
血小板活化因子乙酰水解酶1b催化亚基3(PAFAH1B3)与多种人类疾病相关。然而,其在胃癌中的功能仍不确定。
在癌症基因组图谱(TCGA)和基因型-组织表达泛癌数据中分析PAFAH1B3的表达。使用TCGA临床生存数据评估PAFAH1B3表达与患者预后之间的关联。使用R软件包对PAFAH1B3进行富集分析。此外,通过分析TCGA数据库评估PAFAH1B3表达与免疫细胞浸润之间的相关性。进行CCK8测定和集落形成测定以评估PAFAH1B3对胃癌细胞增殖的影响。使用Transwell测定评估PAFAH1B3对胃癌细胞迁移的影响。进行蛋白质印迹以评估PAFAH1B3在胃癌细胞信号通路中的作用。
PAFAH1B3在包括胃癌在内的多种肿瘤中高表达。高PAFAH1B3表达与参与DNA复制、细胞周期和细胞周期检查点的增殖相关基因集显著相关。进一步分析表明,高PAFAH1B3表达与高M1巨噬细胞和CD8阳性T细胞浸润评分相关。PAFAH1B3敲低抑制了胃癌细胞的增殖、迁移和致癌信号的激活。
我们的研究结果表明,PAFAH1B3可能是胃癌中的一种癌基因。