State Key Laboratory of Oncogenes and Related Genes, Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
State Key Laboratory of Oncogenes and Related Genes, Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hepatobiliary Pancreat Dis Int. 2023 Apr;22(2):169-178. doi: 10.1016/j.hbpd.2022.04.005. Epub 2022 Apr 25.
ADAMTS (a disintegrin and metalloproteinase with thrombospondin-like motifs) family, a group of extracellular multifunctional enzymes, has been proven to play a pivotal role in the tumor. In pancreatic cancer, the role and mechanism of this family remain unclear. The present study aimed to figure out the hub gene of ADAMTSs and explore the exact roles in the prognosis and biological functions in pancreatic ductal adenocarcinoma (PDAC).
We used several databases to analyze the ADAMTS family and then screen out the hub genes. The expression of ADAMTS12 in 106 pairs of PDAC tumors and adjacent normal tissues was examined by immunohistochemistry, and its correlations with clinical parameters were further analyzed. The impacts of ADAMTS12 on the migration of PDAC cells were predicted by gene set enrichment analysis and confirmed by transwell assays. The potential impacts of ADAMTS12 on the epithelial-mesenchymal transition (EMT) were identified by database analysis and experimental proof of real-time quantitative polymerase chain reaction (qPCR) and Western blotting.
Our study found that ADAMTS12 was a crucial gene in PDAC, and it was highly expressed in tumor tissues when compared to that in the adjacent tissues. ADATMS12 had predictive value of a poor prognosis for PDAC. The elevation of ADAMTS12 was parallel to the progression of PDAC. Inhibition of ADAMTS12 suppressed the migration of PDAC cells and interfered with the process of EMT.
ADAMTS12 is a crucial member of ADAMTSs in PDAC and a predictor of poor prognosis. Additionally, based on its impacts on migration and metastasis in PDAC and the relationship with EMT, ADAMTS12 plays a role of an oncogene in PDAC and may be a promising target for treatment.
ADAMTS（解整合素和金属蛋白酶与血小板反应蛋白基序）家族是一组细胞外多功能酶，已被证明在肿瘤中发挥关键作用。在胰腺癌中，该家族的作用和机制尚不清楚。本研究旨在确定 ADAMTSs 的枢纽基因，并探讨其在胰腺导管腺癌（PDAC）中的预后和生物学功能中的确切作用。
我们使用了几个数据库来分析 ADAMTS 家族，然后筛选出枢纽基因。通过免疫组织化学检测 106 对 PDAC 肿瘤和相邻正常组织中 ADAMTS12 的表达，并进一步分析其与临床参数的相关性。通过基因集富集分析预测 ADAMTS12 对 PDAC 细胞迁移的影响，并通过 Transwell 测定进行验证。通过数据库分析和实时定量聚合酶链反应（qPCR）和 Western blot 实验验证 ADAMTS12 对上皮-间充质转化（EMT）的潜在影响。
我们的研究发现 ADAMTS12 是 PDAC 的关键基因，与相邻组织相比，在肿瘤组织中高表达。ADATMS12 对 PDAC 的预后有预测价值。ADAMTS12 的升高与 PDAC 的进展平行。抑制 ADAMTS12 可抑制 PDAC 细胞的迁移并干扰 EMT 过程。
ADAMTS12 是 PDAC 中 ADAMTSs 的关键成员，是预后不良的预测因子。此外，基于其对 PDAC 迁移和转移的影响以及与 EMT 的关系，ADAMTS12 在 PDAC 中发挥癌基因的作用，可能是治疗的有前途的靶点。
