Clinical application of biological markers for treatments of resectable non-small-cell lung cancers.

Clinical application of biological markers for treatments of resectable non-small-cell lung cancers.
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DOI:
10.1038/sj.bjc.6602481
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发表时间:
2005-04-11
影响因子:
8.8
通讯作者:
Yokomise, H
Yokomise, H
中科院分区:
医学1区
文献类型:
--
作者:
Huang, C;Liu, D;Masuya, D;Nakashima, T;Kameyama, K;Ishikawa, S;Ueno, M;Haba, R;Yokomise, H

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我们进行了一项临床研究,以确定用于治疗可切除的非小细胞肺癌(NSCLC)的生物标志物。共研究了173例患者。通过免疫组化,我们评估了Ki-67增殖指数,肿瘤血管,胸苷酸合成酶(TS),血管内皮生长因子(VEGF)-A,VEGF-C和E(上皮)-钙粘蛋白。关于NSCLC患者的生存,肿瘤血管分布(P<0.01)、VEGF-A状态(P=0.03)、VEGF-C状态(P=0.03)和E-cadherin状态(P=0.03)是I期NSCLC患者的重要预后因素。Ki-67增殖指数(P=0.02)和TS状态(P<0.01)是影响II-III期NSCLC患者预后的重要因素。此外,在II-III期NSCLC患者中,UFT(替加氟和尿嘧啶的组合)治疗的TS阴性肿瘤患者的生存率明显优于任何其他患者。与肿瘤血管生成或转移相关的生物标志物可用于检测早期NSCLC中的侵袭性肿瘤。术后化疗可能是必要的,即使在这种肿瘤的第一阶段。相反,肿瘤增殖率和TS状态是用于识别局部晚期NSCLC中侵袭性较低的肿瘤的有用标志物。胸苷酸合成酶表达也是一个有用的标志物,以评估这些肿瘤的UFT为基础的化疗反应。
We performed a clinical study to identify biological markers useful for the treatment of resectable non-small-cell lung cancers (NSCLCs). In all, 173 patients were studied. By immunohistochemistry, we evaluated the Ki-67 proliferation index, tumour vascularity, thymidylate synthase (TS), vascular endothelial growth factor (VEGF)-A, VEGF-C, and E (epithelial)-cadherin. Concerning the survival of NSCLC patients, tumour vascularity (P<0.01), VEGF-A status (P=0.03), VEGF-C status (P=0.03), and E-cadherin status (P=0.03) were significant prognostic factors in patients with stage I NSCLCs. The Ki-67 proliferation index (P=0.02) and TS status (P<0.01) were significant prognostic factors in patients with stage II–III NSCLCs. In patients with stage II–III NSCLCs, furthermore, the survival of UFT (a combination of tegafur and uracil)-treated patients with TS-negative tumours was significantly better than those of any other patients. Biological markers associated with tumour angiogenesis or metastasis are useful for the detection of aggressive tumours among early-stage NSCLCs. Postoperative chemotherapy might be necessary in such tumours even in stage I. In contrast, tumour proliferation rate and TS status are useful markers for identifying less aggressive tumours in locally advanced NSCLCs. Thymidylate synthase expression is also a useful marker to evaluate responsiveness of UFT-based chemotherapy for these tumours.
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