乳酸相关基因PLAU促进胰腺导管腺癌肝转移
Lactate-associated gene PLAU promotes liver metastasis of pancreatic ductal adenocarcinoma.
摘要(中文译文)
胰腺导管腺癌（PDAC）常以致死性肝转移的形式复发，但促进肝脏定植的分子因素仍不清楚。我们将9例原发性PDAC肿瘤和12例肝转移灶的转录组数据（GSE19279和GSE42952）与2420个乳酸相关基因（LRGs）进行整合。采用差异表达基因（DEGs）、加权基因共表达网络分析（WGCNA）和生存分析来鉴定关键基因。利用单细胞数据集（GSE156405）分析枢纽基因。通过shRNA介导的敲低对PLAU进行功能验证，随后进行qRT-PCR、Western blot、CCK-8增殖实验、集落形成实验、Transwell迁移实验以及患者来源的类器官模型。共有102个LRG来源的DEGs富集于细胞运动通路。PLAU是唯一潜在的预后生物标志物（HR = 1.78，P = 0.003）。单细胞RNA测序将PLAU定位于髓系和恶性细胞簇。PLAU沉默显著降低了体外和类器官中的增殖、集落和球体形成（P < 0.01）。PLAU是一种乳酸相关的、细胞内在的PDAC肝转移驱动因子，代表了一个有前景的代谢-表观遗传靶点，用于预防或治疗肝脏复发。
Abstract
Pancreatic ductal adenocarcinoma (PDAC) often recurs as lethal liver metastasis, but the molecular factors that facilitate hepatic colonization remain unclear. Transcriptomic data from 9 primary PDAC tumors and 12 liver metastases (GSE19279 and GSE42952) were integrated with 2420 lactate-related genes (LRGs). Differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), and survival analysis were employed to identify key genes. Analyzing hub genes using a single-cell dataset (GSE156405). Functional validation of PLAU was performed by shRNA-mediated knockdown, followed by qRT-PCR, Western blot, CCK-8 proliferation, colony formation, Transwell migration assays, and patient-derived organoid models. A total of 102 LRG-derived DEGs were enriched in cell-motility pathways. PLAU emerged as the only potential prognostic biomarker (HR = 1.78, P = 0.003). Single-cell RNA sequencing localized PLAU to myeloid and malignant clusters. PLAU silencing significantly reduced proliferation, colony, and sphere formation both in vitro and in organoids (P < 0.01). PLAU, a lactate-associated, cell-intrinsic driver of PDAC liver metastasis, represents a promising metabolic-epigenetic target for preventing or treating hepatic relapse.
如何引用
AMA
Xinghe Liao, Fenglin Zhang, Qun Huang, Xiaorui Wu, Jiangang Zhao, Zhou Zhou, et al. Lactate-associated gene PLAU promotes liver metastasis of pancreatic ductal adenocarcinoma.. Computational biology and chemistry. 2026; doi:10.1016/j.compbiolchem.2026.109075.
APA
Xinghe Liao, Fenglin Zhang, Qun Huang, Xiaorui Wu, Jiangang Zhao, Zhou Zhou, et al (2026). Lactate-associated gene PLAU promotes liver metastasis of pancreatic ductal adenocarcinoma.. Computational biology and chemistry. https://doi.org/10.1016/j.compbiolchem.2026.109075
GB/T 7714
Xinghe Liao, Fenglin Zhang, Qun Huang, Xiaorui Wu, Jiangang Zhao, Zhou Zhou, et al. Lactate-associated gene PLAU promotes liver metastasis of pancreatic ductal adenocarcinoma.[J]. Computational biology and chemistry, 2026 doi:10.1016/j.compbiolchem.2026.109075.
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