iNOS-dependent DNA damage in patients with malignant fibrous histiocytoma in relation to prognosis
iNOS-dependent DNA damage in patients with malignant fibrous histiocytoma in relation to prognosis
复制标题
DOI：
10.1111/j.1349-7006.2006.00376.x
复制
发表时间：
2007-02-01
期刊：
影响因子：
5.7
通讯作者：
Kawanishi, Shosuke
中科院分区：
文献类型：
--
作者：
Hoki, Yoko;Hiraku, Yusuke;Kawanishi, Shosuke
恶性纤维组织细胞瘤是最常见的软组织肉瘤之一。MFH被认为是一种伴有炎症反应的病变。在慢性炎症过程中，由炎症细胞产生的活性氮和氧被认为通过引起DNA损伤而参与致癌作用。8-硝基鸟嘌呤是在慢性炎症过程中形成的致突变硝化DNA损伤。我们研究了硝化DNA损伤是否与MFH患者的预后有关。我们对25例MFH患者的临床标本进行了免疫组化分析，以检测DNA损伤的分布和炎症相关分子的表达，包括诱导型一氧化氮合酶（iNOS）、核因子-κ B（NF-κ B）和环氧合酶-2（考克斯-2）。我们还分析了DNA损伤或这些基因的表达与MFH患者预后的相关性。免疫组织化学染色显示，8-硝基鸟嘌呤和8-氧代-7，8-二氢-2 '-脱氧鸟苷（8-oxodG）的形成，一种氧化DNA损伤，在死亡患者的MFH组织标本中比在活患者中发生的程度要大得多。iNOS、NF-κ B和考克斯-2与8-硝基鸟嘌呤在MFH组织中共定位。值得注意的是，使用Kaplan-Meier方法的统计分析表明，强8-硝基鸟嘌呤染色与不良预后相关。总之，8-硝基鸟嘌呤似乎不仅参与MFH的启动和促进，而且还参与MFH的进展，因此可以用作评估癌症患者预后的有希望的生物标志物。
Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas. MFH has been proposed to be a lesion accompanied with inflammatory responses. During chronic inflammation, reactive nitrogen and oxygen species generated from inflammatory cells are considered to participate in carcinogenesis by causing DNA damage. 8-nitroguanine is a mutagenic nitrative DNA lesion formed during chronic inflammation. We examined whether nitrative DNA damage is related to the prognosis of MFH patients. We performed immunohistochemical analyses to examine the distribution of DNA damage and the expression of inflammation-related molecules including inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-kappa B), and cyclooxygenase-2 (COX-2) in clinical specimens from 25 patients with MFH. We also analyzed the correlation of DNA damage or the expression of these genes with the prognosis of MFH patients. Immunohistochemical staining revealed that the formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidative DNA lesion, occurred to a much greater extent in MFH tissue specimens from deceased patients than in live patients. iNOS, NF-kappa B and COX-2 were colocalized with 8-nitroguanine in MFH tissues. It is noteworthy that the statistical analysis using the Kaplan-Meier method demonstrated strong 8-nitroguanine staining to be associated with a poor prognosis. In conclusion, 8-nitroguanine appears to participate in not only the initiation and promotion of MFH, but also in the progression of MFH, and could therefore be used as a promising biomarker to evaluate the prognosis of cancer patients.