Luo Zhengdong, Wang Lei, Shang Ziqi, Guo Qining, Liu Qi, Zhang Mengjiao, Li Tingting, Wang Yifeng, Zhang Yanli, Zhang Yi, Zhang Xin
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012, China.
Department of Orthodontics, Qilu Hospital of Shandong University, Jinan 250012, China.
Transl Oncol. 2022 Aug;22:101462. doi: 10.1016/j.tranon.2022.101462. Epub 2022 May 27.
Pancreatic adenocarcinoma (PAAD) has become one of the deadliest malignancies in the world. Since necroptosis plays a crucial role in regulating the immune system, it is necessary to develop novel prognostic biomarkers associated with necroptosis and explore its potential role in PAAD. The transcriptome RNA-seq data of PAAD were downloaded from the TCGA and GTEx databases. A prognostic signature was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression, and its prognostic value was evaluated by nomogram and validated in an independent GEO cohort. We identified a total of 24 differentially expressed NRGs in PAAD, and constructed a prognostic signature with 5 NRGs, which showed good performance in predicting the prognosis of PAAD patients. The ROC curves for 1-, 3-, and 5-year survival rate were 0.652, 0.778, and 0.817, respectively. This prognostic signature showed consistent prognosis prediction in an independent patient cohort. Furthermore, the correlations between 5-NRGs signature and TMB, MSI, histopathological classification, immune infiltration, immune types, and immunomodulators were all significant. Notably, the expression profiles of the five NRGs in exosomes of serum were consistent with their expression in tumor tissues. These data suggested that the 5-NRGs signature is a promising biomarker for predicting the prognosis of PAAD.
胰腺腺癌（PAAD）已成为世界上最致命的恶性肿瘤之一。由于坏死性凋亡在调节免疫系统中起着关键作用，因此有必要开发与坏死性凋亡相关的新型预后生物标志物，并探索其在PAAD中的潜在作用。从TCGA和GTEx数据库下载PAAD的转录组RNA-seq数据。通过最小绝对收缩和选择算子（LASSO）Cox回归构建预后特征，并通过列线图评估其预后价值，并在独立的GEO队列中进行验证。我们在PAAD中总共鉴定出24个差异表达的坏死性凋亡相关基因（NRGs），并构建了一个包含5个NRGs的预后特征，该特征在预测PAAD患者的预后方面表现良好。1年、3年和5年生存率的ROC曲线分别为0.652、0.778和0.817。该预后特征在独立患者队列中显示出一致的预后预测。此外，5-NRGs特征与肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、组织病理学分类、免疫浸润、免疫类型和免疫调节剂之间的相关性均具有统计学意义。值得注意的是，血清外泌体中5个NRGs的表达谱与其在肿瘤组织中的表达一致。这些数据表明，5-NRGs特征是预测PAAD预后的一个有前景的生物标志物。
