KPNA4在胰腺癌中高表达并且与不良预后相关

High expression of KPNA4 is associated with poor prognosis in pancreatic cancer

目的 分析KPNA4在胰腺癌中的临床意义和潜在作用机制。方法 联合TCGA、GTEx和GEO数据库评估KPNA4在肿瘤和正常组织中的表达水平,收集临床样本通过免疫组化进一步验证。通过Cox分析和生存分析评估KPNA4对胰腺癌患者预后的影响,生物信息学分析用于预测KPNA4的相关功能和潜在机制。结果 生物信息学分析和免疫组化结果显示KPNA4的mRNA和蛋白表达水平在胰腺癌组织中均上调(P<0.05),相关性分析显示其mRNA表达水平与肿瘤大小(r=0.261,P<0.001)和淋巴结转移(r=0.193,P<0.05)正相关。生存分析显示KPNA4的mRNA高表达组患者的生存时间短于低表达组(P<0.001)。Cox多因素分析显示KPNA4是胰腺癌患者预后的独立危险因素(95%CI 1.132~2.808,P<0.05)。富集分析显示KPNA4参与了TGF-β信号通路、细胞外基质受体相互作用等多种肿瘤相关的生物学过程。结论 KPNA4在胰腺癌中异常上调,与患者的肿瘤大小和淋巴结转移呈正相关,并且预示着不良预后。KPNA4可能是胰腺癌诊断和治疗的潜在生物标记物。

objective To analyze the clinical significance and potential mechanism of Karyopherin alpha 4(KPNA4) in pancreatic cancer. Methods The expression levels of KPNA4 in tumor and normal tissues were evaluated with TCGA, GTEx and GEO databases, and immunohistochemistry was used to further confirm differential expression of KPNA4 in clinical samples. Cox analysis and survival analysis were used to evaluate the prognostic significance of KPNA4 in pancreatic cancer patients, and bioinformatics analysis was used to predict the related functions and underlying mechanisms of KPNA4. Results Bioinformatics analysis and immunohistochemical results showed that the mRNA and protein expression levels of KPNA4 were up-regulated in pancreatic cancer tissues(P<0.05). Correlation analysis showed that KPNA4 mRNA expression level was positively correlated with tumor size(r=0.261, P<0.001) and lymph node metastasis(r=0.193, P<0.05). Survival analysis showed that the survival time of patients in KPNA4 mRNA high expression group was shorter than that in low expression group(P<0.001). Cox multivariate analysis showed that KPNA4 was an independent risk factor for patient prognosis(95%CI 1.132-2.808, P<0.05). Enrichment analysis showed that KPNA4 was involved in a variety of tumor-related biological processes such as TGF-β signaling pathway and extracellular matrix receptor interaction. Conclusion KPNA4 is abnormally up-regulated in pancreatic cancer and positively correlated with tumor size and lymph node metastasis in pancreatic cancer patients. High expression of KPNA4 predicts poor prognosis. KPNA4 may be a potential biomarker for pancreatic cancer diagnosis and treatment.