Identification of postoperative adjuvant chemotherapy responders in non-small cell lung cancer by novel biomarker
Identification of postoperative adjuvant chemotherapy responders in non-small cell lung cancer by novel biomarker
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DOI：
10.1002/ijc.21172
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发表时间：
2005-11-10
影响因子：
6.4
通讯作者：
Ikeda, N
中科院分区：
文献类型：
--
作者：
Hirano, T;Kato, H;Ikeda, N
据报道，与单纯完全切除术相比，非小细胞肺癌（NSCLC）的顺铂（CDDP）辅助化疗可使5年生存率提高5-15%。关于良好反应者预选的信息的重要性已变得越来越明显。我们研究的目的是建立一个预选的良好反应者的CDDP为基础的辅助化疗。采用双向聚丙烯酰胺凝胶电泳（2DE）技术，对亲本株（1169和PC 14肺癌培养细胞）和耐药株（CDDP）的蛋白质表达进行比较。免疫组化，我们评估了与CDDP耐药相关的蛋白质表达和基于铂类的术后辅助化疗的临床效果之间的关系，使用126个切除的NCLC材料。我们在双向电泳凝胶上检测到两种改变表达水平的多肽。氨基酸序列分析表明，这些多肽分别为网织红蛋白（RCN）和谷胱甘肽-S-转移酶-π（GST-pi）。双向电泳结果显示，随着CDDP耐药的发生，RCN中GST-pi的表达逐渐减少，而GST-pi的表达逐渐增加。H69 CDDP抗性株的RCN-转染子表现出介于亲本株和CDDP抗性株之间的中间敏感性。RCN阳性病例仅在根治性切除术后接受以铂为基础的术后辅助化疗的病例中显示出统计学显著更好的无病生存率（p = 0.007）。此外，RCN阳性和GST-π阴性的病例显示统计学显著更好的结局（p = 0.0150）。在没有术后辅助化疗的病例中，结果与这些表达之间没有关系。RCN和GST-pi的评估可能从个体化术后治疗的角度提供有价值的信息，术后治疗策略。(c)2005 Wiley-Liss，Inc.
Cisplatin-based (CDDP-based) adjuvant chemotherapy of non-small cell lung cancer (NSCLC) was reported to yield 5-15% improvement in 5-year survival compared to complete resection alone. The importance of information concerning preselection of good responders has become increasingly evident. The purpose of our study is the establishment of a preselection of good responders for CDDP-based adjuvant chemotherapy. We investigated protein expressions comparing intensity between parent strains (1169 and PC14 lung cancer cultured cells) and resistant strains against CDDP using 2-dimensional polyacrylamide gel electrophoresis (2DE). Immunohistochemically, we evaluated the relationship between protein expression associated with CDDP-resistance and the clinical effects of platinum-based postoperative adjuvant chemotherapy using 126 surgically-resected NCLC materials. We detected 2 kinds of polypeptides that changed expression levels on 2-DE gels. The analyses of the amino acid sequence showed that these polypeptides were reticulocalbin (RCN) and glutathione-S-transferase-pi (GST-pi). The 2-DE analysis showed decreased expression in RCN and overexpression in GST-pi with the acquisition of CDDP-drug resistance. RCN-transfectant of H69 CDDP-resistant strain showed intermediate sensitivity between the parent strain and the CDDP-resistant strain. RCN-positive cases showed a statistically significant better disease-free survival only in the cases receiving postoperative platinum-based adjuvant chemotherapy after curative resection (p = 0.007). In addition, cases that were both RCN-positive and GST-pi-negative showed a statistically significantly better outcome (p = 0.0150). In the cases without postoperative adjuvant chemotherapy no relationship between the outcome and these expressions was seen. The evaluation of RCN and GST-pi might provide valuable information concerning postoperatively therapeutic strategy from the standpoint of individualized postoperative therapy. (c) 2005 Wiley-Liss, Inc.