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Identification of an extracellular vesicle-related gene signature in the prediction of pancreatic cancer clinical prognosis

机译:鉴别胰腺癌临床预后预测中的细胞外囊泡相关基因签名

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摘要

Although extracellular vesicles (EVs) in body fluid have been considered to be ideal biomarkers for cancer diagnosis and prognosis, it is still difficult to distinguish EVs derived from tumor tissue and normal tissue. Therefore, the prognostic value of tumor-specific EVs was evaluated through related molecules in pancreatic tumor tissue. NA sequencing data of pancreatic adenocarcinoma (PAAD) were acquired from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). EV-related genes in pancreatic cancer were obtained from exoRBase. Protein–protein interaction (PPI) network analysis was used to identify modules related to clinical stage. CIBERSORT was used to assess the abundance of immune and non-immune cells in the tumor microenvironment. A total of 12 PPI modules were identified, and the 3-PPI-MOD was identified based on the randomForest package. The genes of this model are involved in DNA damage and repair and cell membrane-related pathways. The independent external verification cohorts showed that the 3-PPI-MOD can significantly classify patient prognosis. Moreover, compared with the model constructed by pure gene expression, the 3-PPI-MOD showed better prognostic value. The expression of genes in the 3-PPI-MOD had a significant positive correlation with immune cells. Genes related to the hypoxia pathway were significantly enriched in the high-risk tumors predicted by the 3-PPI-MOD. External databases were used to verify the gene expression in the 3-PPI-MOD. The 3-PPI-MOD had satisfactory predictive performance and could be used as a prognostic predictive biomarker for pancreatic cancer.
机译:虽然体液中的细胞外囊泡(EVS)被认为是癌症诊断和预后的理想生物标志物,但仍然难以区分衍生自肿瘤组织和正常组织的EV。因此,通过胰腺肿瘤组织中的相关分子评估肿瘤特异性EVS的预后值。从癌症基因组Atlas(TCGA)和国际癌症基因组联盟(ICGC)中获得胰腺腺癌(Paad)的Na测序数据。胰腺癌中的EV相关基因是从Exorbase获得的。蛋白质 - 蛋白质相互作用(PPI)网络分析用于鉴定与临床阶段相关的模块。 Cibersort用于评估肿瘤微环境中的免疫和非免疫细胞的丰度。鉴定了总共12个PPI模块,并且基于随机纲要包识别了3-PPI-MOD。该模型的基因涉及DNA损伤和修复和细胞膜相关途径。独立的外部验证队列表明,3-PPI-MOD可以显着分类患者预后。此外,与由纯基因表达构成的模型相比,3-PPI-MOD显示出更好的预后值。 3-PPI-MOM中基因的表达与免疫细胞具有显着的正相关。与缺氧途径相关的基因显着富含3-PPI-MOD预测的高风险肿瘤。外部数据库用于验证3-PPI-MOD中的基因表达。 3-PPI-MOD具有令人满意的预测性能,可用作胰腺癌的预后预测生物标志物。

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