Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Kolling Institute of Medical Research, University of Sydney, St Leonards, Sydney, New South Wales, Australia.
Cancer Sci. 2024 May;115(5):1446-1458. doi: 10.1111/cas.16124. Epub 2024 Mar 4.
Pancreatic ductal adenocarcinoma (PDAC) patients have late presentation at the time of diagnosis and a poor prognosis. Metal dyshomeostasis is known to play a role in cancer progression. However, the blood and tissue metallome of PDAC patients has not been assessed. This study aimed to determine the levels of essential and toxic metals in the serum and pancreatic tissue from PDAC patients. Serum samples were obtained from PDAC patients before surgical resection. Tissue (tumor and adjacent normal pancreas) were obtained from the surgically resected specimen. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis was performed to quantify the levels of 10 essential and 3 toxic metals in these samples. Statistical analysis was performed to identify dysregulated metals in PDAC and their role as potential diagnostic and prognostic biomarkers. Significantly decreased serum levels of magnesium, potassium, calcium, iron, zinc, selenium, arsenic, and mercury and increased levels of molybdenum were shown to be associated with PDAC. There were significantly decreased levels of zinc, manganese and molybdenum, and increased levels of calcium and selenium in the pancreatic tumor tissue compared with the adjacent normal pancreas. Notably, lower serum levels of calcium, iron, and selenium, and higher levels of manganese, were significantly associated with a poor prognosis (i.e., overall survival) in PDAC patients. In conclusion, this is the first study to comprehensively assess the serum and tissue metallome of PDAC patients. It identified the association of metals with PDAC diagnosis and prognosis.
胰腺导管腺癌 (PDAC) 患者在诊断时表现为晚期，预后较差。金属代谢失调已知在癌症进展中起作用。然而，PDAC 患者的血液和组织金属组尚未得到评估。本研究旨在确定 PDAC 患者血清和胰腺组织中必需和有毒金属的水平。在手术切除前从 PDAC 患者获得血清样本。从手术切除的标本中获得组织（肿瘤和相邻正常胰腺）。使用电感耦合等离子体质谱 (ICP-MS) 分析来定量这些样本中的 10 种必需和 3 种有毒金属的水平。进行了统计分析，以确定 PDAC 中失调的金属及其作为潜在诊断和预后生物标志物的作用。结果表明，与 PDAC 相关的是血清镁、钾、钙、铁、锌、硒、砷和汞水平显著降低，钼水平显著升高。与相邻正常胰腺相比，胰腺肿瘤组织中的锌、锰和钼水平显著降低，钙和硒水平显著升高。值得注意的是，血清钙、铁和硒水平降低，锰水平升高与 PDAC 患者的预后（即总生存率）显著相关。总之，这是第一项全面评估 PDAC 患者血清和组织金属组的研究。它确定了金属与 PDAC 诊断和预后的关联。
