NUP37的泛癌分析及其在胰腺癌中的功能和预后价值

Pan-cancer Analysis of NUP37 and Its Function,Prognostic Value in Pancreatic Cancer

目的 对核通道蛋白37 kDa(nucleoporin 37 kDa, NUP37)进行泛癌分析,观察NUP37对胰腺癌(pancreatic adenocarcinoma, PAAD)细胞SW1990增殖、侵袭及迁移的影响。探讨NUP37在PAAD中的表达差异、临床意义及预后价值,并预测NUP37在PAAD中可能的作用机制。方法 从癌症基因组图谱(The Cancer Genome Atlas, TCGA)数据库下载与整理NUP37在33种肿瘤及11 057例样本的mRNA表达水平及生存预后相关数据,统计分析NUP37在泛癌中的表达及预后情况。分别采用5-乙炔基-2′脱氧尿嘧啶核苷(5-ethynyl-2′-deoxyuridine, EdU)免疫荧光实验、Transwell实验、划痕实验检测过表达NUP37和沉默NUP37对SW1990细胞增殖、侵袭、迁移的影响。利用基因表达水平值的交互式分析平台(Gene Expression Profiling Interactive Analysis, GEPIA)数据库分析NUP37在PAAD中的表达及预后。从TCGA数据库获取PAAD患者NUP37表达水平、临床病理特征及生存时间等数据,统计分析NUP37表达水平与PAAD患者临床病理特征及预后的关系。通过基因组富集分析(Gene Set Enrichment Analysis, GSEA)预测NUP37在PAAD中可能调控的信号通路。结果 泛癌分析结果显示,NUP37在膀胱尿路上皮癌(bladder urothelial carcinoma, BUC)、乳腺浸润癌(breast invasive carcinoma, BRCA)、胆管癌(cholangiocarcinoma, CHOL)等17种肿瘤中高表达(P<0.05),且NUP37高表达预示着PAAD、肺腺癌(lung adenocarcinoma, LUAD)、肝细胞性肝癌(liver hepatocellular carcinoma, LIHC)等7种肿瘤患者的生存状态更差(P<0.05)。GEPIA数据库分析结果表明,NUP37在PAAD组织中的mRNA表达水平显著高于正常胰腺组织(P<0.05),且NUP37高表达组PAAD患者的总生存期显著低于低表达组患者(P<0.05),预后更差。EdU免疫荧光实验检测结果显示,过表达NUP37促进PAAD SW1990细胞增殖(P<0.01),沉默NUP37则抑制PAAD SW1990细胞增殖(P<0.01)。Transwell实验检测结果显示,过表达NUP37促进PAAD SW1990细胞侵袭(P<0.001),沉默NUP37则抑制PAAD SW1990细胞侵袭(P<0.001)。划痕实验检测结果显示,过表达NUP37促进PAAD SW1990细胞迁移(P<0.01),沉默NUP37则抑制PAAD SW1990细胞迁移(P<0.01)。TCGA数据库分析结果显示,NUP37表达水平、N分期是PAAD患者预后的独立危险因素(P<0.05)。GSEA研究结果显示,NUP37 mRNA高表达样本富集到细胞周期、蛋白酶体、DNA复制、错配修复等相关基因集(P<0.05)。结论 NUP37在PAAD组织中高表达并预示PAAD患者的不良预后。NUP37促进PAAD细胞增殖、侵袭及迁移。NUP37可能是PAAD和泛癌的潜在癌基因和预后生物标志物。

Objective To investigate pan-cancer analysis of nucleoporin 37 kDa(NUP37), and to observe the effects of NUP37 on the proliferation, invasion and migration of pancreatic adenocarcinoma(PAAD) cell SW1990. Moreover, to investigate the expression difference, clinical significance and prognostic value of NUP37 in PAAD, and to predict the possible mechanism of NUP37 in PAAD. Methods mRNA expression levels and survival prognosis related data of NUP37 in 33 types of tumors and 11 057 samples were downloaded and organized from The Cancer Genome Atlas(TCGA) database, and the expression and prognosis of NUP37 in pan cancer were statistically analyzed. The effects of over expresson NUP37 and silencing NUP37 on the proliferation, invasion and migration of SW1990 cells were detected by 5-ethynyl-2′-deoxyuridine(EdU) immunofluorescence assay, Transwell assay and scratch assay. The expression and prognosis of NUP37 in PAAD were analyzed by Gene Expression Profiling Interactive Analysis(GEPIA) database. NUP37 expression level, clinicopathological characteristics and survival time of PAAD patients were obtained from TCGA database, and the relationship between NUP37 expression level and clinicopathological characteristics, prognosis of PAAD patients were statistically analyzed. The possible regulatory signaling pathway of NUP37 in PAAD was predicted by Gene Set Enrichment Analysis(GSEA). Results The pan cancer analysis results showed that NUP37 was highly expressed in 17 kinds of tumors, including bladder urothelium carcinoma(BUC), breast invasive carcinoma(BRCA) cholangiocarcinoma(CHOL), etc.(P<0.05), and the high expression of NUP37 indicated that the survival status of patients with 7 kinds of tumors was worse, including PAAD, lung adenocarcinoma(LUAD), liver hepatocellular carcinoma(LIHC), etc.(P<0.05). GEPIA database analysis results showed that the mRNA expression level of NUP37 PAAD tissue was significantly higher than that in normal pancreatic tissue(P<0.05), and the overall survival period of patients with PAAD in the NUP37 high expression group was significantly lower than that in the low expression group(P<0.05), which had worse prognosis. The detection results of EdU immunofluorescence assay showed that overexpression of NUP37 promoted the proliferation of PAAD SW1990 cell(P<0.01);silencing NUP37 inhibited the proliferation of PAAD SW1990 cell(P<0.01). The detection results of Transwell assay showed that overexpression of NUP37 promoted the invasion of PAAD SW1990 cell(P<0.001);silencing NUP37 inhibited the invasion of PAAD SW1990 cell(P<0.001). The detection results of scratch assay showed that overexpression of NUP37 promoted the migration of PAAD SW1990 cell(P<0.01), silencing NUP37 inhibited the migration of PAAD SW1990 cell(P<0.01). TCGA database analysis results showed that NUP37 expression level and N stage were independent risk factors for the prognosis of PAAD patients(P<0.05). GSEA research results showed that NUP37 mRNA overexpression samples were enriched to cell cycle, proteasome, DNA replication, mismatch repair and other related gene sets(P<0.05). Conclusion NUP37 is highly expressed in PAAD tissue and indicates a poor prognosis of PAAD patients. NUP37 promotes the proliferation, invasion and migration of PAAD cells. NUP37 may be a potential oncogene and prognostic biomarker for PAAD and pan-cancer.