Deng Yanyao, Hu Hai, Xiao Le, Cai Ting, Gao Wenzhe, Zhu Hongwei, Wang Shuai, Liu Jixing
Department of Rehabilitation, The First Hospital of Changsha, Changsha, Hunan Province, China.
Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, China.
J Oncol. 2022 Apr 11;2022:8259951. doi: 10.1155/2022/8259951. eCollection 2022.
Epithelial-mesenchymal transition (EMT) can promote carcinoma progression by multiple mechanisms; many studies demonstrated the invasiveness of pancreatic adenocarcinoma (PAAD) associated with the EMT, but how it acts through an lncRNA-dependent manner is unknown. Here, we investigated 146 samples from The Cancer Genome Atlas (TCGA) and 92 samples from the International Cancer Genome Consortium (ICGC). By gene set variation analysis (GSVA) and weighted correlation network analysis (WGCNA), we explored the EMT-related long noncoding RNAs (EMTlnc). Then, we performed univariate Cox regression analysis to screen their prognostic value for PAAD. The least absolute contraction and selection operator (LASSO) Cox regression was used to establish EMT-related lncRNA prognostic signal (EMT-LPS). In addition, we established a competitive endogenous ceRNA network. Then, we identified 33 prognostic EMTlnc as prognostic lncRNAs and established an EMT-LPS which showed strong prognostic ability in stratification analysis. By corresponding risk scores, patients were divided into low-risk and high-risk subgroups. Principal component analysis (PCA) showed that these subgroups had individual EMT status. Enrichment analysis showed that in the high-risk subgroup, biological processes, pathways, and hallmarks related to malignant tumors are more common. What is more, we constructed a nomogram that had powerful ability to predict the overall survival rate (OS) of PAAD patients in two datasets. So, EMT-LPS are a principal element in PAAD's carcinoma progression and may help us in choosing the way of prognosis assessment and provide some clues to design the new drugs for PAAD.
上皮-间质转化（EMT）可通过多种机制促进癌进展；许多研究表明胰腺腺癌（PAAD）的侵袭性与EMT相关，但尚不清楚其如何通过长链非编码RNA（lncRNA）依赖性方式发挥作用。在此，我们研究了来自癌症基因组图谱（TCGA）的146个样本和来自国际癌症基因组联盟（ICGC）的92个样本。通过基因集变异分析（GSVA）和加权基因共表达网络分析（WGCNA），我们探索了与EMT相关的长链非编码RNA（EMTlnc）。然后，我们进行单变量Cox回归分析以筛选它们对PAAD的预后价值。使用最小绝对收缩和选择算子（LASSO）Cox回归建立与EMT相关的lncRNA预后信号（EMT-LPS）。此外，我们建立了一个竞争性内源性ceRNA网络。然后，我们将33个预后EMTlnc鉴定为预后lncRNAs，并建立了一个在分层分析中显示出强大预后能力的EMT-LPS。通过相应的风险评分，将患者分为低风险和高风险亚组。主成分分析（PCA）表明这些亚组具有个体EMT状态。富集分析表明，在高风险亚组中，与恶性肿瘤相关的生物学过程、途径和特征更为常见。此外，我们构建了一个列线图，该列线图在两个数据集中具有强大的预测PAAD患者总生存率（OS）的能力。因此，EMT-LPS是PAAD癌进展的主要因素，可能有助于我们选择预后评估方法，并为设计PAAD新药提供一些线索。
