Usefulness of monitoring the circulating Krebs von den Lungen-6 levels to predict the clinical outcome of patients with advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors
Usefulness of monitoring the circulating Krebs von den Lungen-6 levels to predict the clinical outcome of patients with advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors
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DOI：
10.1002/ijc.23411
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发表时间：
2008-06-01
影响因子：
6.4
通讯作者：
Kohno, Nobuoki
中科院分区：
文献类型：
--
作者：
Ishikawa, Nobuhisa;Hattori, Noboru;Kohno, Nobuoki
Krebs von den Lungen-6（KL-6）是一种高分子量糖蛋白，属于人MUC 1粘蛋白的范畴。据报道，KL-6可作为间质性肺炎的敏感标志物;然而，最近的研究表明，它也可用作肿瘤标志物。为了进一步阐明循环KL-6在肺癌中的临床病理学意义，我们监测了晚期非小细胞肺癌（NSCLC）患者的循环KL-6水平，并分析了这些水平与EGFR-TKI治疗临床结局之间的相关性。发现疾病进展（PD）患者的循环KL-6预处理水平显著高于疾病控制（部分缓解（PR）和疾病稳定（SD））患者。多变量分析显示循环KL-6水平是总生存期和无进展生存期的独立预后因素。除了这些观察结果外，我们还发现EGFR-TKI治疗开始后2周循环KL-6水平相对于基线的变化可以非常精确地区分PD病例与PR或SD患者以及NSCLC患者中EGFR-TKI的临床结局。这些结果表明，监测NSCLC患者的循环KL-6水平对于选择接受EGFR-TKI治疗的患者和预测EGFR-TKI的临床结局都是有效的。此外，研究结果表明，循环KL-6水平可用作NSCLC患者的临床相关生物标志物，特别是那些EGFR-TKI治疗的候选人。(c)2008 Wiley-Liss，Inc.
Krebs von den Lungen-6 (KL-6) is a high molecular weight glycoprotein classified in the category of human MUC1 mucin. KL-6 has been reported to serve as a sensitive marker for interstitial pneumonia; however, recent studies have suggested that it can also be used as a tumor marker as its origin shows. To further elucidate the clinicopathological significance of circulating KL-6 in lung cancer, we monitored the circulating KL-6 levels in advanced nonsmall cell lung cancer (NSCLC) patients and analyzed the association between these levels and the clinical outcome of EGFR-TKI treatment. The pretreatment levels of circulating KL-6 were found to be significantly higher in progressive disease (PD) patients than disease-controlled (partial response (PR) and stable disease (SD)) patients. Multivariate analyses revealed the circulating KL-6 level to be an independent prognostic factor for overall survival as well as progression-free survival. In addition to these observations, we found that changes in circulating KL-6 levels at 2 weeks after the start of EGFR-TKI treatment from the baseline could quite precisely discriminate PD cases from PR or SD patients and the clinical outcome of EGFR-TKI in NSCLC patients. These results indicate that the monitoring of circulating KL-6 levels in NSCLC patients is effective for both selecting patients to be treated with EGFR-TKI and predicting the clinical outcome of EGFR-TKI. In addition, the findings suggest that the circulating KL-6 level could be used as a clinically relevant bio-marker in patients with NSCLC, particularly those who are candidates for EGFR-TKI treatment. (c) 2008 Wiley-Liss, Inc.