Identification of biomarkers for predicting nasopharyngeal carcinoma response to radiotherapy by proteomics.
Radiotherapy is the primary treatment for nasopharyngeal cancer (NPC), but radioresistance remains a serious obstacle to successful treatment in many cases. To identify the proteins involved in this resistance and to evaluate their potential for predicting NPC response to radiotherapy, we first established a radioresistant subclone cell line (CNE2-IR) derived from NPC cell line CNE2 by treating the cells with five rounds of sublethal ionizing radiation. Proteomics was then performed to compare the protein profiles of CNE2-IR and CNE2, and a total of 34 differential proteins were identified. Among them, 14-3-3sigma and Maspin were downregulated and GRP78 and Mn-SOD were upregulated in the radioresistant CNE2-IR compared with control CNE2, which was conformed by Western blot. Immunohistochemistry was performed to detect the expression of the four validated proteins in the 39 radioresistant and 51 radiosensitive NPC tissues and their value for predicting NPC response to radiotherapy were evaluated by receiver operating characteristic analysis. The results showed that the downregulation of 14-3-3sigma and Maspin and the upregulation of GRP78 and Mn-SOD were significantly correlated with NPC radioresistance and the combination of the four proteins achieved a sensitivity of 90% and a specificity of 88% in discriminating radiosensitive from radiaoresistant NPC. Furthermore, the resistance to ionizing radiation can be partially reversed by the overexpression of 14-3-3sigma in the CNE2-IR. The data suggest that 14-3-3sigma, Maspin, GRP78, and Mn-SOD are potential biomarkers for predicting NPC response to radiotherapy and their dysregulation may be involved in the radioresistance of NPC.
Feng
Xue-Ping
XP
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Hunan Province, China.
Yi
Hong
H
Li
Mao-Yu
MY
Li
Xin-Hui
XH
Yi
Bin
B
Zhang
Peng-Fei
PF
Li
Cui
C
Peng
Fang
F
Tang
Can-E
CE
Li
Jian-Ling
JL
Chen
Zhu-Chu
ZC
Xiao
Zhi-Qiang
ZQ
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D005092:Exonucleases; D005095:Exoribonucleases; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D009363:Neoplasm Proteins; D040901:Proteomics / Q000379:methods; D011836:Radiation Tolerance; D015843:Serpins / Q000096:biosynthesis; D013482:Superoxide Dismutase / Q000096:biosynthesis
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; C085344:SERPIN-B5; D015843:Serpins; D013482:Superoxide Dismutase; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human