Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, China.
Front Immunol. 2024 Sep 23;15:1435593. doi: 10.3389/fimmu.2024.1435593. eCollection 2024.
Pancreatic cancer is an extremely malignant tumor. PVT1 and MYC signaling has been considered as a therapeutic target recently. Nonetheless, the prognostic values and critical regulatory networks of PVT1-MYC duet in pancreatic cancer remain unclear. Firstly, we identified PVT1-MYC duet-related genes using public databases. Then we analyzed our Hi-C and ChIP-seq data to confirm PVT1-MYC duet. We performed LASSO regression and multivariate Cox regression analysis to build a prognostic model whose effectiveness and robustness were validated by Cox regression, ROC analysis, calibration curve, and nomogram. Besides, we conducted functional enrichment analyses, mutation profiles analyses and the immune features analyses to compare low- and high-risk group. Functional enrichment analyses revealed that several terms associated with cancer progression were enriched in the high-risk group. Mutation profile analysis showed that high-risk group had higher tumor mutation burden, and immune analysis demonstrated high-risk group had more immunosuppressive tumor microenvironment. Finally, we detected PVT1 expression in pancreatic cancer and paracancer tissues from the PUMCH cohort, which showed that PVT1 was significantly upregulated in pancreatic cancer and associated with invasion, metastasis, and poor prognosis. We further performed transwell and proliferation assays and found that PVT1, CDC6, and COL17A1 could promote migration or proliferation of PDAC cells. This study constructed a prognostic model based on three PVT1-MYC duet-related genes, which had a significant potential in predicting the prognosis and tumor microenvironment of pancreatic cancer. These results suggested that targeting PVT1-MYC duet or its regulatory processes could be a therapeutic option with great interests.
胰腺癌是一种极其恶性的肿瘤。PVT1 和 MYC 信号通路最近被认为是治疗靶点。然而，PVT1-MYC 二聚体在胰腺癌中的预后价值和关键调控网络仍不清楚。首先，我们使用公共数据库鉴定了 PVT1-MYC 二聚体相关基因。然后，我们分析了我们的 Hi-C 和 ChIP-seq 数据来证实 PVT1-MYC 二聚体。我们进行了 LASSO 回归和多变量 Cox 回归分析，构建了一个预后模型，通过 Cox 回归、ROC 分析、校准曲线和列线图验证了其有效性和稳健性。此外，我们进行了功能富集分析、突变谱分析和免疫特征分析，以比较低风险组和高风险组。功能富集分析显示，高风险组中富集了几个与癌症进展相关的术语。突变谱分析显示，高风险组具有更高的肿瘤突变负担，免疫分析表明高风险组具有更多的免疫抑制肿瘤微环境。最后，我们检测了来自 PUMCH 队列的胰腺癌和癌旁组织中的 PVT1 表达，结果表明 PVT1 在胰腺癌中显著上调，并与侵袭、转移和不良预后相关。我们进一步进行了 Transwell 和增殖实验，发现 PVT1、CDC6 和 COL17A1 可以促进 PDAC 细胞的迁移或增殖。本研究构建了一个基于三个 PVT1-MYC 二聚体相关基因的预后模型，该模型在预测胰腺癌的预后和肿瘤微环境方面具有显著的潜力。这些结果表明，针对 PVT1-MYC 二聚体或其调控过程可能是一种很有前途的治疗选择。
