Prognostic value of phosphorylated Raf kinase inhibitory protein at serine 153 and its predictive effect on the clinical response to radiotherapy in nasopharyngeal carcinoma.

Prognostic value of phosphorylated Raf kinase inhibitory protein at serine 153 and its predictive effect on the clinical response to radiotherapy in nasopharyngeal carcinoma.
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153位丝氨酸磷酸化Raf激酶抑制蛋白的预后价值及其对鼻咽癌放疗临床反应的预测作用。

DOI:
10.1186/s13014-016-0696-5
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发表时间:
2016-09-20
期刊:
Radiation oncology (London, England)
影响因子:
--
通讯作者:
Zhao H
Zhao H
中科院分区:
其他
文献类型:
--
作者:
Li S;Liu T;Mo W;Hou Q;Zhou Y;Liu M;He Z;Liu Z;Chen Q;Wang H;Guo X;Xia W;Zeng M;Zhao H

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放射治疗是治疗鼻咽癌的有效方法。然而,放射抵抗诱导的局部复发仍然是治疗失败的主要原因。因此,应在治疗前开发放射敏感性指标,以筛选放射抵抗患者。已有研究表明Raf激酶抑制蛋白(RKIP)与鼻咽癌的预后和放射敏感性有关。然而,p-Ser 153 RKIP(RKIP在丝氨酸153位残基的磷酸化形式)表达与鼻咽癌患者的放射效应和预后的关系尚未阐明。因此,磷酸化RKIP在NPC中的这些临床意义还有待描述。p-Ser 153 RKIP对局部无复发生存期(LRRFS)的影响首先在一组初次诊断时无远处转移的NPC患者中进行了回顾性分析。他们只接受根治性调强放疗。180例患者入组正在进行的配对研究。根据放射敏感性和放射耐受性标准将患者重新分为放射耐受组和放射敏感组。两组患者在放射敏感性相关因素方面相匹配。放射治疗前应用免疫组化法检测鼻咽癌组织芯片中p-Ser 153 RKIP的表达。分析p-Ser 153 RKIP表达与放疗疗效的关系。在这项研究中,建立了一个回顾性队列,其中733例接受根治性放疗。使用该队列,我们验证了通过免疫组化染色在治疗前NPC组织微阵列中观察到的p-Ser 153 RKIP表达是LRRFS和OS的独立预后因素;我们还证实了p-Ser 153 RKIP表达阳性的地方病患者在局部无复发生存期方面仅受益于照射。共180例患者入组配对研究。两组在放射敏感性相关因素方面匹配良好。基于p-Ser 153 RKIP表达,我们预测了以下数据:80.0%的敏感性,73.3%的特异性,76.7%的准确性,75.0%的阳性预测值,和78.6%的阴性预测值。我们的研究结果首次揭示了p-Ser 153 RKIP阳性表达是一个有利的预后因素。与鼻咽癌放射敏感性呈正相关。p-Ser 153 RKIP也可作为一种有效性和真实性良好的生物分子标记物用于NPC相关临床放射敏感性的初步筛选。本文的在线版本(doi:10.1186/s13014-016-0696-5)包含补充材料,可供授权用户使用。
Radiation is an effective treatment against nasopharyngeal carcinoma (NPC). However, radioresistance-induced locoregional recurrence remains as a major cause of treatment failure. Therefore, radiosensitivity indicators prior to treatment should be developed to screen radioresistant patients. Previous studies revealed that RKIP (Raf kinase inhibitor protein) is associated with NPC prognosis and radiosensitivity. However, the relationship of p-Ser153 RKIP (RKIP in a phosphorylated form at residue serine153) expression with the effect of radiation and prognosis of NPC patients is not elucidated. Thus, these clinical implication of the phosphorylated RKIP in NPC has yet to be described. The effect of p-Ser153 RKIP on locoregional relapse-free survival (LRRFS) was first analyzed in a retrospective cohort of NPC patients without distant metastasis at initial diagnosis. They received radical intensity-modulated radiotherapy alone. Of 180 patients were enrolled in the ongoing matched pair study. The patients were re-classified into radioresistant group or radiosensitive group on the basis of the specified criteria. Patients in the two groups were matched in terms of radiosensitivity-related factors. p-Ser153 RKIP was examined by immunohistochemical staining on a NPC tissue microarray before radiotherapy. The relationship between the expression of p-Ser153 RKIP and the effect of radiotherapy was also analyzed. In this study, a retrospective cohort with 733 cases who received radical radiotherapy alone was established. Using the cohort, we validated that the p-Ser153 RKIP expression observed through immunohistochemical staining in a pretreatment NPC tissue microarray was an independent prognostic factor of LRRFS and OS; we also confirmed that endemic patients with a positive p-Ser153 RKIP expression benefited from irradiation alone in terms of locoregional relapse-free survival. A total of 180 patients were enrolled in a matched pair study. Both groups were well matched in terms of radiosensitivity-related factors. On the basis of the p-Ser153 RKIP expression, we predicted the following data: 80.0 % sensitivity, 73.3 % specificity, 76.7 % accuracy, 75.0 % positive predictive value, and 78.6 % negative predictive value. Our results revealed for the first time that positive p-Ser153 RKIP expression was a favorable prognostic factor. It was also positively correlated with the radiosensitivity of NPC. p-Ser153 RKIP could also be used as a biomolecular marker with good availability and authenticity to preliminarily screen NPC-related clinical radiosensitivity. The online version of this article (doi:10.1186/s13014-016-0696-5) contains supplementary material, which is available to authorized users.
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