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核因子-κB表达可预测皮肤黑色素瘤患者的总生存期。

Nuclear factor-κB expression is predictive of overall survival in patients with cutaneous melanoma.

作者信息

Murtas Daniela, Piras Franca, Minerba Luigi, Ugalde Jorge, Piga Michela, Maxia Cristina, Perra Maria Teresa, Sirigu Paola

机构信息

Department of Cytomorphology, University of Cagliari, 09042 Monserrato (CA).

出版信息

Oncol Lett. 2010 Jul;1(4):633-639. doi: 10.3892/ol_00000112. Epub 2010 Jul 1.

DOI:10.3892/ol_00000112
PMID:22966356
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3436470/
Abstract

Nuclear factor (NF)- κB is one of the most important transcription factors that plays a crucial role in the regulation of a wide spectrum of genes involved in modulating the cell cycle, apoptosis, cell growth, angiogenesis, inflammation and the tissue invasiveness of highly malignant cells. NF-κB activity has been found to be constitutively elevated in a number of human tumors from either a haematological or solid origin, such as melanomas. In several studies, NF-κB activation was shown to be an adverse prognostic factor, and in melanoma it was proposed as an event that promotes tumor progression. This study aimed to evaluate whether NF-κB activation in tumor tissues, assessed by the expression of the NF-κB p65 subunit, has an effect on the survival of melanoma patients. The expression of NF-κB was immunohistochemically investigated, and the correlation with survival was analyzed. Furthermore, the immunostaining for p53 and survivin was evaluated, and the relationship of these apoptotic and anti-apoptotic factors with NF-κB expression was analyzed. Kaplan-Meier analysis showed that patients with low levels of NF-κB in the nuclei of tumor cells had a significantly longer survival compared to those with high levels. Multivariate analysis confirmed the predictive value of nuclear NF-κB, showing that its expression maintains significance after the model was adjusted using clinicopathological factors. The results demonstrate the correlation of NF-κB p65 nuclear staining with the disease-specific 5-year survival of melanoma patients and suggest that nuclear NF-κB p65 may be promising as an early independent prognostic factor in patients with primary cutaneous melanoma.

摘要

核因子(NF)-κB是最重要的转录因子之一,在调控参与调节细胞周期、细胞凋亡、细胞生长、血管生成、炎症以及高恶性细胞的组织侵袭性的广泛基因中发挥关键作用。已发现NF-κB活性在多种血液系统或实体来源的人类肿瘤(如黑色素瘤)中持续升高。在多项研究中,NF-κB激活被证明是一个不良预后因素,在黑色素瘤中它被认为是促进肿瘤进展的一个事件。本研究旨在评估通过NF-κB p65亚基表达评估的肿瘤组织中NF-κB激活是否对黑色素瘤患者的生存有影响。采用免疫组织化学方法研究NF-κB的表达,并分析其与生存的相关性。此外,评估p53和生存素的免疫染色,并分析这些凋亡和抗凋亡因子与NF-κB表达的关系。Kaplan-Meier分析表明,肿瘤细胞核中NF-κB水平低的患者与水平高的患者相比,生存期显著更长。多变量分析证实了核NF-κB的预测价值,表明在使用临床病理因素调整模型后其表达仍具有显著性。结果证明了NF-κB p65核染色与黑色素瘤患者疾病特异性5年生存率的相关性,并表明核NF-κB p65可能有望成为原发性皮肤黑色素瘤患者的早期独立预后因素。

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本文引用的文献

1
Tumour suppression by p53: the importance of apoptosis and cellular senescence.p53介导的肿瘤抑制:细胞凋亡和细胞衰老的重要性。
J Pathol. 2009 Sep;219(1):3-15. doi: 10.1002/path.2584.
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NF-kappaB activation through the alternative pathway correlates with chemoresistance and poor survival in extranodal NK/T-cell lymphoma, nasal type.通过替代途径激活核因子-κB与鼻型结外NK/T细胞淋巴瘤的化疗耐药及不良生存相关。
Jpn J Clin Oncol. 2009 Jul;39(7):418-24. doi: 10.1093/jjco/hyp037. Epub 2009 Apr 24.
3
Cleaved caspase-3 and nuclear factor-kappaB p65 are prognostic factors in metastatic serous ovarian carcinoma.裂解的半胱天冬酶-3和核因子-κB p65是转移性浆液性卵巢癌的预后因素。
Hum Pathol. 2009 Jun;40(6):795-806. doi: 10.1016/j.humpath.2008.10.019. Epub 2009 Jan 20.
4
NF-KappaB expression correlates with apoptosis and angiogenesis in clear cell renal cell carcinoma tissues.核因子-κB表达与透明细胞肾细胞癌组织中的细胞凋亡和血管生成相关。
J Exp Clin Cancer Res. 2008 Oct 19;27(1):53. doi: 10.1186/1756-9966-27-53.
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Transcription factors: their potential as targets for an individualized therapeutic approach to cancer.转录因子:其作为癌症个体化治疗方法靶点的潜力。
Cancer Gene Ther. 2009 Feb;16(2):103-12. doi: 10.1038/cgt.2008.73. Epub 2008 Oct 10.
6
Combinations of apoptosis and cell-cycle control biomarkers predict the outcome of human melanoma.细胞凋亡与细胞周期控制生物标志物的组合可预测人类黑色素瘤的预后。
Oncol Rep. 2008 Aug;20(2):271-7.
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NF-kappaB and cancer-identifying targets and mechanisms.核因子-κB与癌症识别靶点及机制
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High expression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis.RelA/p65的高表达与胰腺癌中核因子-κB依赖性信号通路的激活相关,并标志着预后不良的患者群体。
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