PAFAH1B3 预测肺腺癌不良预后并促进其进展。
PAFAH1B3 predicts poor prognosis and promotes progression in lung adenocarcinoma.
机构信息
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Department of Respiratory and Critical Care Medicine, The Affiliated Wuxi Second People's Hospital of Nanjing Medical University, Wuxi, 214000, Jiangsu, China.
出版信息
BMC Cancer. 2022 May 9;22(1):525. doi: 10.1186/s12885-022-09617-x.
BACKGROUND
Recently, increasing evidence has indicated that platelet-activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3) plays an important role in several cancers. However, its role in lung adenocarcinoma (LUAD) has not been reported until now.
METHODS
The expression of PAFAH1B3 in LUAD was determined by using the Gene Expression Profiling Interactive Analysis (GEPIA) database and real-time PCR (RT-PCR), western blot and immunohistochemical (IHC) analyses. A chi-square test was used to investigate the correlation between PAFAH1B3 expression and clinical parameters. Cox regression and Kaplan-Meier analysis were performed to analyze the prognostic value of PAFAH1B3. The CCK-8 assay, clone formation assay, transwell invasion assay and flow cytometry were conducted to detect cell proliferation, clone formation, invasion and the cell cycle. The xenograft tumor model was constructed to explore the function of PAFAH1B3 in vivo. Western blot and IHC analyses were performed to detect epithelial-to-mesenchymal transition (EMT)-related markers. Immune Cell Abundance Identifier (ImmuneCellAI) and IHC analyses were used to analyze the effect of PAFAH1B3 on immune cell infiltration.
RESULTS
Our study showed that the expression of PAFAH1B3 was upregulated in LUAD tissues and cells compared with noncancerous tissues and cells. Additionally, the results indicated that the expression of PAFAH1B3 was positively correlated with distant metastasis, TNM stage and poor clinical outcome and it was an independent prognostic risk factor for LUAD. In addition, silencing PAFAH1B3 suppressed cell proliferation, colony formation, and invasion and increased the cell population in the G0-G1 phases in vitro. Furthermore, our results showed that knockdown of PAFAH1B3 increased the epithelial marker E-cadherin level and decreased the mesenchymal marker N-cadherin level in vitro and in vivo. We also proved that PAFAH1B3 downregulation inhibited tumorigenesis and neutrophil infiltration in the xenograft tumor model.
CONCLUSION
Our studies indicate that PAFAH1B3, a prognostic risk factor, promotes proliferation, invasion and EMT and affects immune infiltrates in LUAD.
背景
最近，越来越多的证据表明血小板激活因子乙酰水解酶 1b 催化亚基 3（PAFAH1B3）在多种癌症中发挥着重要作用。然而，其在肺腺癌（LUAD）中的作用至今尚未报道。
方法
使用基因表达谱分析交互分析（GEPIA）数据库和实时 PCR（RT-PCR）、Western blot 和免疫组织化学（IHC）分析来确定 LUAD 中 PAFAH1B3 的表达。使用卡方检验来研究 PAFAH1B3 表达与临床参数之间的相关性。Cox 回归和 Kaplan-Meier 分析用于分析 PAFAH1B3 的预后价值。CCK-8 测定、克隆形成测定、Transwell 侵袭测定和流式细胞术用于检测细胞增殖、克隆形成、侵袭和细胞周期。构建异种移植肿瘤模型以在体内探索 PAFAH1B3 的功能。Western blot 和 IHC 分析用于检测上皮间质转化（EMT）相关标志物。免疫细胞丰度鉴定（Immune Cell Abundance Identifier，ImmuneCellAI）和 IHC 分析用于分析 PAFAH1B3 对免疫细胞浸润的影响。
结果
我们的研究表明，与非癌组织和细胞相比，PAFAH1B3 在 LUAD 组织和细胞中的表达上调。此外，结果表明，PAFAH1B3 的表达与远处转移、TNM 分期和不良临床结局呈正相关，并且是 LUAD 的独立预后风险因素。此外，沉默 PAFAH1B3 抑制了细胞的体外增殖、集落形成和侵袭，并增加了细胞在 G0-G1 期的比例。此外，我们的结果表明，PAFAH1B3 的敲低降低了体外和体内的上皮标志物 E-钙黏蛋白水平，并增加了间充质标志物 N-钙黏蛋白水平。我们还证明，PAFAH1B3 的下调抑制了异种移植肿瘤模型中的肿瘤发生和中性粒细胞浸润。
结论
我们的研究表明，PAFAH1B3 作为一个预后风险因素，促进了 LUAD 中的增殖、侵袭和 EMT，并影响了免疫浸润。
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