title: Prognostic value of phosphorylated Raf kinase inhibitory protein at serine 153 and its predictive effect on the clinical response to radiotherapy in nasopharyngeal carcinoma.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiation Oncology, The Affiliated Hospital of Guilin Medical University, No. 15 Lequn Road, Guilin, 541004, Guangxi Zhuang Autonomous Region, People's Republic of China.
authors.forename: Siwei
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Oncology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, No.46 Chongxin Road, Guilin, 541004, Guangxi Zhuang Autonomous Region, People's Republic of China.
authors.forename: Taowen
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pathology, The Affiliated Hospital of Guilin Medical University, No. 15 Lequn Road, Guilin, 541004, Guangxi Zhuang Autonomous Region, People's Republic of China.
authors.forename: Wenfa
authors.initials: W
authors.lastname: Mo
authors.affiliation: Department of Pathology, The Affiliated Hospital of Guilin Medical University, No. 15 Lequn Road, Guilin, 541004, Guangxi Zhuang Autonomous Region, People's Republic of China.
authors.forename: Qiaoyan
authors.initials: Q
authors.lastname: Hou
authors.affiliation: Department of Pathology, The Affiliated Hospital of Guilin Medical University, No. 15 Lequn Road, Guilin, 541004, Guangxi Zhuang Autonomous Region, People's Republic of China.
authors.forename: Yingqiong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, The Affiliated Hospital of Guilin Medical University, No. 15 Lequn Road, Guilin, 541004, Guangxi Zhuang Autonomous Region, People's Republic of China.
authors.forename: Meilian
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, The Affiliated Hospital of Guilin Medical University, No. 15 Lequn Road, Guilin, 541004, Guangxi Zhuang Autonomous Region, People's Republic of China.
authors.forename: Zhoukai
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, The Affiliated Hospital of Guilin Medical University, No. 15 Lequn Road, Guilin, 541004, Guangxi Zhuang Autonomous Region, People's Republic of China.
authors.forename: Zhengchun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, The Affiliated Hospital of Guilin Medical University, No. 15 Lequn Road, Guilin, 541004, Guangxi Zhuang Autonomous Region, People's Republic of China.
authors.forename: Qiuqiu
authors.initials: Q
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No.651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No.651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.|Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in Southern China, No.651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No.651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.|Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in Southern China, No.651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
authors.forename: Weixiong
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in Southern China, No.651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
authors.forename: Musheng
authors.initials: M
authors.lastname: Zeng
authors.affiliation: 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. zhaohaiyun111111@sina.com.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D002277:Carcinoma; D015331:Cohort Studies; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy*; D049488:Phosphatidylethanolamine Binding Protein / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D011878:Radiotherapy / Q000379:methods*; D012008:Recurrence; D012189:Retrospective Studies; D012694:Serine / Q000737:chemistry; D046888:Tissue Array Analysis
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D012694:Serine
keywords: Nasopharyngeal carcinoma; Phosphorylated Raf kinase inhibitor protein (pRKIP); Prediction; Prognosis; Radiotherapy; Sensitivity