Ulukaya Engin, Yilmaztepe Arzu, Akgoz Semra, Linder Stig, Karadag Mehmet
Biochemistry Department of Medical School of Uludag University, Bursa, Turkey, and Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institute and Hospital, Stockholm, Sweden.
Lung Cancer. 2007 Jun;56(3):399-404. doi: 10.1016/j.lungcan.2007.01.015. Epub 2007 Feb 20.
Caspase-cleaved cytokeratin 18 fragments (M30 antigen) can be detected in the circulation of patients with carcinoma and are believed to reflect cell death of tumors of epithelial origin. M30 antigens cleaved at Asp396 are detected using an epitope-specific antibody (M30 antibody). We here measured the levels of such fragments in patients with lung cancer (n=60), patients with benign lung disease (n=22) and healthy control subjects (n=32). A statistically significant difference was observed between these groups (p<0.001; Kruskal-Wallis). Basal M30 antigen levels were evaluated with regard to their predictive power of survival. The best cut-off value for M30 antigen level for the prediction of death was 43.8 U/L. Patients with basal M30 antigen levels higher than 43.8 U/L had significantly shorter median survival than those with lower basal M30 antigen levels (p=0.013; hazard ratio: 3.9) (95% CI=1.3-11.4). To determine whether cytotoxic therapy increases serum M30 antigen in lung cancer patients, we monitored the levels of M30 antigen in 18 lung cancer patients before chemotherapy and after 24 and 48 h. An approximately four-fold increase in M30 antigen levels was observed at 48 h (p<0.001). These results suggest as a first time that serum M30 antigen might be used as a novel biomarker for prediction of survival as well as for monitoring the efficiency of chemotherapy in lung cancer patients.
在癌症患者的循环系统中可以检测到半胱天冬酶切割的细胞角蛋白18片段(M30抗原),据信其反映了上皮来源肿瘤的细胞死亡。使用表位特异性抗体(M30抗体)检测在天冬氨酸396处切割的M30抗原。我们在此测量了肺癌患者(n = 60)、良性肺病患者(n = 22)和健康对照者(n = 32)中此类片段的水平。这些组之间观察到统计学上的显著差异(p<0.001;Kruskal-Wallis检验)。评估了基础M30抗原水平对生存的预测能力。预测死亡的M30抗原水平的最佳临界值为43.8 U/L。基础M30抗原水平高于43.8 U/L的患者的中位生存期明显短于基础M30抗原水平较低的患者(p = 0.013;风险比:3.9)(95%置信区间=1.3 - 11.4)。为了确定细胞毒性疗法是否会增加肺癌患者血清M30抗原水平,我们监测了18例肺癌患者化疗前以及化疗后24小时和48小时的M30抗原水平。在48小时时观察到M30抗原水平增加了约四倍(p<0.001)。这些结果首次表明血清M30抗原可能用作预测肺癌患者生存以及监测化疗疗效的新型生物标志物。