Identification of Biomarkers for Predicting Nasopharyngeal Carcinoma Response to Radiotherapy by Proteomics

Abstract

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, 14-3-3σ 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 14-3-3σ 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 14-3-3σ in the CNE2-IR. The data suggest that 14-3-3σ, 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. Cancer Res; 70(9); 3450-62. ©2010 AACR.

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

“…A quantitative score was performed by adding the score of staining area and the score of staining intensity for each case to assess the protein expression levels as previously described. 47 At least 10 high-power fields were chosen randomly and 41000 cells were counted for each section. First, a quantitative score was performed by estimating the percentage of staining-positive cells: 0, no staining of cells in any microscopic field; 1+,o30% of cells stained positive; 2+, between 30 and 60% stained positive; and 3+, 460% stained positive.…”

Protein expression of nucleophosmin, annexin A3 and nm23-H1 correlates with human nasopharyngeal carcinoma radioresistance in vivo

“…Previous studies have screened for DEPs associated with radioresistance in NPC (4,10). One study identified seven upregulated genes in radioresistant subclones of CNE2.…”

“…This may be due to distinct tissue specificity or the different methods used. Although several radioresistant subclones of NPC have been established (3,4), no animal experiments have been reported thus far. As described previously (3), we have also established a subclone (CNE-2R) by exposing CNE-2 cells to a cumulative radiation dose of 64 Gy.…”

Downregulation of Annexin A1 is correlated with radioresistance in nasopharyngeal carcinoma

“…Therefore, NPC poses one of the most severe public health problems in these areas (1). The disease tends to be more sensitive to ionizing radiation (IR) than other head and neck cancers and, therefore, the primary treatment for patients with NPC is radiotherapy (2,3). Although the technology for radiotherapy has been improved, its therapeutic effects on NPC are unchanged.…”

“…The main reason for this is the existence of radioresistant cells in NPC tissues. These cells not only show resistance to radiation, but they also exhibit an increased invasive ability following radiotherapy (2,4,5). Some patients with NPC present with local recurrence and distant metastases following radiotherapy due to radioresistance.…”