Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
Br J Cancer. 2010 Feb 2;102(3):577-82. doi: 10.1038/sj.bjc.6605494. Epub 2010 Jan 5.
Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or predictive biomarker utility in a range of solid tumour types. Characterisation of baseline levels of circulating full length and cleaved CK18 specifically in patients with pancreatic cancer.
Plasma samples from 103 patients with pancreatic cancer stored at -80 degrees C were assayed for M65 and M30 levels. The median (inter-quartile range (IQR)) duration of plasma storage was 34 (23-57) months. Patients with metastatic disease (n=19) were found to have greater median (IQR) M65 levels (1145 (739-1698) U l(-1)) compared with the locally advanced (n=20; 748 (406-1150) U l(-1)) and resected (n=64; 612 (331-987) U l(-1)) patients (P=0.002). Elevated M65 levels were associated with poorer overall survival on univariate (P<0.001) but not multivariate (P=0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum-bilirubin levels (P<0.001) and the duration of plasma storage (P<0.001).
Baseline plasma CK18 levels in pancreatic cancer are affected by the presence of obstructive jaundice and prolonged plasma storage. Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors.
酶联免疫吸附试验检测全长（M65）和/或半胱天冬酶切割（M30）细胞角蛋白 18（CK18）分别来自坏死和/或凋亡的上皮细胞，在多种实体肿瘤类型中可能具有预后或预测生物标志物的作用。本研究旨在专门对胰腺癌患者进行基线水平的循环全长和裂解 CK18 的特征描述。
对 103 例储存于-80℃的胰腺癌患者的血浆样本进行 M65 和 M30 水平检测。血浆储存的中位数（四分位距（IQR））时间为 34（23-57）个月。与局部晚期（n=20；748（406-1150）U l（-1））和可切除（n=64；612（331-987）U l（-1））患者相比，转移性疾病（n=19）患者的 M65 水平中位数（IQR）更高（1145（739-1698）U l（-1））（P=0.002）。在单因素分析中，M65 水平升高与总生存不良相关（P<0.001），但在多因素分析中（P=0.202）则无相关性。M65 浓度与同期血清胆红素水平（P<0.001）和血浆储存时间（P<0.001）显著相关。
在胰腺癌中，基础血浆 CK18 水平受阻塞性黄疸和延长的血浆储存的影响。在进行胰腺癌的临床生物标志物研究时，需要考虑到这些潜在的混杂因素，因此有必要对连续的 CK18 水平进行研究。
