Department of Radiation Oncology, Shaanxi Provincial People's Hospital, Xi'an, China.
Department of Orthopaedics, Shaanxi Provincial People's Hospital, Xi'an, China.
Medicine (Baltimore). 2024 Mar 1;103(9):e37322. doi: 10.1097/MD.0000000000037322.
Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with poor prognosis. However, the relationship between cuproptosis-related genes (CRGs) and its competing endogenous RNA (ceRNA) network with the prognosis of PAAD patients remains unclear. To investigate this relationship, we calculated the difference in CRGs between PAAD tissues and normal tissues using the 'limma' R package. Additionally, we employed least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct a prognostic signature for CRGs. Survival analysis of patients with PAAD was performed using Kaplan-Meier analysis. Furthermore, we used bioinformatics tools to screen for CRGs-related MicroRNA (miRNA) and lncRNAs. To validate these findings, we conducted real-time quantitative polymerase chain reaction (RT-qPCR), CCK-8, colony formation, and Transwell assays to assess the effect of DLAT in vitro. Our results revealed a cuproptosis-related prognostic signature consisting of 3 prognostic genes (DLAT, LIAS, and LIPT1). Notably, patients with a high-risk score for the CRGs signature exhibited poor prognosis in terms of overall survival (OS) (P < .05). The receiver operating characteristic (ROC) curve was used to evaluate the prognostic signature of CRGs. The results showed that the 1-year, 3-year, and 5-year area under the curve values for predicting OS were 0.62, 0.66, and 0.79, respectively. Additionally, the CRGs-related ceRNA network revealed the regulatory axis of LINC00857/has-miR-1179/DLAT in PAAD. In vitro experiments demonstrated that knockdown of LINC00857 and DLAT inhibited the growth and invasion of PAAD cells. This study identified a CRG-related prognostic signature consisting of 3 biomarkers (DLAT, LIAS, and LIPT1) for PAAD. Furthermore, ceRNA network analysis suggested the involvement of the LINC00857/has-miR-1179/DLAT axis in the development of PAAD. Overall, this study provides theoretical support for the investigation of diagnostic and prognostic biomarkers as well as potential therapeutic targets in PAAD.
胰腺导管腺癌（PAAD）是一种预后不良的高度恶性肿瘤。然而，铜死亡相关基因（CRGs）与 PAAD 患者预后的竞争内源性 RNA（ceRNA）网络之间的关系尚不清楚。为了研究这种关系，我们使用 'limma' R 包计算了 PAAD 组织和正常组织之间 CRGs 的差异。此外，我们采用最小绝对收缩和选择算子（LASSO）Cox 回归分析构建了 CRGs 的预后特征。使用 Kaplan-Meier 分析对 PAAD 患者进行生存分析。此外，我们使用生物信息学工具筛选 CRGs 相关的 MicroRNA（miRNA）和 lncRNA。为了验证这些发现，我们进行了实时定量聚合酶链反应（RT-qPCR）、CCK-8、集落形成和 Transwell 测定，以评估 DLAT 的体外作用。我们的结果显示了一个由 3 个预后基因（DLAT、LIAS 和 LIPT1）组成的铜死亡相关预后特征。值得注意的是，具有高风险评分的 CRGs 特征的患者在总生存（OS）方面预后不良（P ＜ 0.05）。接收器操作特征（ROC）曲线用于评估 CRGs 的预后特征。结果表明，预测 OS 的 1 年、3 年和 5 年 AUC 值分别为 0.62、0.66 和 0.79。此外，CRGs 相关的 ceRNA 网络揭示了 LINC00857/has-miR-1179/DLAT 在 PAAD 中的调节轴。体外实验表明，敲低 LINC00857 和 DLAT 抑制了 PAAD 细胞的生长和侵袭。本研究确定了由 3 个生物标志物（DLAT、LIAS 和 LIPT1）组成的与 PAAD 相关的 CRG 预后特征。此外，ceRNA 网络分析表明，LINC00857/has-miR-1179/DLAT 轴参与了 PAAD 的发展。总体而言，本研究为研究 PAAD 的诊断和预后生物标志物以及潜在的治疗靶点提供了理论支持。
