Prognostic value of phosphorylated Raf kinase inhibitory protein at serine 153 and its predictive effect on the clinical
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RESEARCH
Open Access
Prognostic value of phosphorylated Raf kinase inhibitory protein at serine 153 and its predictive effect on the clinical response to radiotherapy in nasopharyngeal carcinoma Siwei Li1†, Taowen Liu2†, Wenfa Mo3, Qiaoyan Hou3, Yingqiong Zhou3, Meilian Liu4, Zhoukai He4, Zhengchun Liu4, Qiuqiu Chen4, Hua Wang5, Xiang Guo5,6, Weixiong Xia5,6, Musheng Zeng6 and Haiyun Zhao7*
Abstract Background: 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. Methods: 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. Results: 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. (Continued on next page)
* Correspondence: [email protected] † Equal contributors 7 Department of Otorhinolaryngology, Head and Neck Surgery, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, No.46 Chongxin Road, Guilin 541004, Guangxi Zhuang Autonomous Region, People’s Republic of China Full list of author information is available at the end of the article © 2016 The
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