Up-regulation of peroxiredoxin 1 in lung cancer and its implication as a prognostic and therapeutic target
Up-regulation of peroxiredoxin 1 in lung cancer and its implication as a prognostic and therapeutic target
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DOI：
10.1158/1078-0432.ccr-07-4457
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发表时间：
2008-04-15
影响因子：
11.5
通讯作者：
Park, Young-Mee
中科院分区：
文献类型：
--
作者：
Kim, Joo-Heon;Bogner, Paul N.;Park, Young-Mee
Peroxiredoxin 1和2是Prx（或Prdx）蛋白家族的高度同源成员。Prx 1和Prx 2在几种人类癌症中升高，这似乎赋予了增加的治疗抗性和侵袭性表型。本研究旨在检测Prx 1和Prx 2在非小细胞肺癌（NSCLC）中的表达谱，并测试其在预测患者生存期方面的预后价值。为了深入了解NSCLC中Prx 1和Prx 2表达的调控机制，在来自NCI-60 panel Affyoung数据库集的NSCLC细胞系中检查了它们各自的转录谱，并使用基于计算机的多重序列比对分析来研究这两个基因的启动子组成。对235例I期至IV期NSCLC标本进行Prx 1和Prx 2免疫组化分析。结果与结论：非小细胞肺癌细胞株中Prx 1基因的转录水平高于Prx 2基因，且两基因的上游调控序列存在明显差异。在多变量考克斯模型中，死亡的相对风险随着Prx 1表达水平的增加而增加（P = 0.036），与其他与生存相关的临床病理变量无关。Prx 2与生存率之间未观察到统计学显著相关性。这些结果提示，Prx 1在NSCLC中可能具有与Prx 2不同的功能和调控机制，Prx 1可能成为NSCLC新的预后生物标志物和治疗靶点。
Purpose: Peroxiredoxin 1 and 2 are highly homologous members of the Prx (or Prdx) protein family. Prx1 and Prx2 are elevated in several human cancers, and this seems to confer increased treatment resistance and aggressive phenotypes. This study was undertaken to examine the expression profiles of Prx1 and Prx2 in non -small cell lung cancer (NSCLC), and to test their prognostic value in predicting patient survival.Experimental Design: To gain insight into the regulatory mechanisms of Prx1 and Prx2 expression in NSCLC, their respective transcript profiles were examined in NSCLC cell lines from the NCI-60 panel Affymetrix database sets, and the promoter compositions of the two genes were investigated using computer-based multiple sequence alignment analyses. Immunohistochemical analyses of Prx1 and Prx2 were done on a total of 235 NSCLC specimens with stage I through IV disease. The expression profiles of Prx1 and Prx2 in tumor specimens, and their associations with survival, were investigated.Results and Conclusion: The levels of prx1 transcript were higher than those of prx2 in NSCLC cell lines, and the upstream regulatory sequences of the two genes display striking differences. The relative risk of death increased as Prx1 expression levels increased (P = 0.036) in a multi-variate Cox model, independent of other clinicopathologic variables associated with survival. No statistically significant correlation was observed between Prx2 and survival. These results suggest that Prx1 may possess unique functions and regulatory mechanisms in NSCLC which are not shared with Prx2, and that Prx1 may serve as a new prognostic biomarker and therapeutic target in NSCLC.