Asparagine synthetase expression and its potential prognostic value in patients with NK/T cell lymphoma

  • Authors:
    • Yaqing Li
    • Xudong Zhang
    • Tengpeng Hu
    • Lijuan Han
    • Ruping Li
    • Jianguo Wen
    • Mingzhi Zhang
  • View Affiliations

  • Published online on: June 6, 2014     https://doi.org/10.3892/or.2014.3237
  • Pages: 853-859
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Abstract

Natural killer (NK)/T cell lymphoma usually shows a highly aggressive clinical course and the overall prognosis is poor. At present, there are no standard therapeutic regimens for this disease. Although chemotherapeutic protocols containing L-asparaginase (L-Asp) or pegaspargase (PEG‑Asp) have improved the efficacy of treatment, some patients are resistant to L-Asp or PEG-Asp. Previous studies demonstrated that the elevated expression of asparagine synthetase (ASNS) is correlated with the resistance to L-Asp or PEG-Asp and may also affect the prognosis in some types of tumors, but the expression level and clinical significance of ASNS in NK/T cell lymphoma remain unknown. Therefore, we investigated the expression and clinical significance of ASNS in lymphoma cell lines and patients with NK/T cell lymphoma. Firstly, we detected PEG-Asp and L-Asp activity using MTT assay and expression of ASNS using real-time PCR in the 7 lymphoma cell lines. Secondly, we used branched DNA-liquidchip technology (bDNA-LCT) for detecting ASNS mRNA in formalin-fixed, paraffin-embedded tissue sections in 50 cases of NK/T cell lymphoma and in 12 cases of nasal polyps and chronic rhinitis. Moreover, we analyzed the correlations between the expression of ASNS and the sensitivity to L-Asp and PEG-Asp in 7 lymphoma cell lines and with clinicopathological features and prognosis of NK/T cell lymphoma patients who used chemotherapy containing L-Asp and PEG-Asp. There was a marked difference in the sensitivity to L-Asp and PEG-Asp of the 7 lymphoma cell lines. YTS and SNK-6 cells were highly sensitive to PEG-Asp and had relatively low levels of ASNS mRNA expression. Hut-78, Jurkat and Karpas 299 cells were naturally resistant to PEG-Asp, and the ASNS expression levels were extremely high. The expression level of ASNS was relatively low in the NK/T cell lymphoma tissue compared to levels in the nasal polyps and chronic rhinitis (0.480±0.307 vs. 0.739±0.267; P=0.009). ASNS expression level was associated with III-IV tumor stage (P=0.041) and a high International Prognostic Index (P=0.018) in patients with NK/T cell lymphoma. The NK/T cell lymphoma patients with higher ASNS expression had a reduced median survival time when compared with the survival of patients with low ASNS expression (P=0.033). Cox regression test showed that the ASNS expression level is an independent prognostic factor for NK/T cell lymphoma patients. In conclusion, the expression of ASNS was closely related with the sensitivity of lymphoma cell lines to L-Asp and PEG-Asp in vitro and also had a certain effect on the survival of NK/T cell lymphoma patients. In conclusion, high ASNS expression in NK/T cell lymphoma is correlated with worse clinicopathological features.
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August-2014
Volume 32 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Li Y, Zhang X, Hu T, Han L, Li R, Wen J and Zhang M: Asparagine synthetase expression and its potential prognostic value in patients with NK/T cell lymphoma. Oncol Rep 32: 853-859, 2014
APA
Li, Y., Zhang, X., Hu, T., Han, L., Li, R., Wen, J., & Zhang, M. (2014). Asparagine synthetase expression and its potential prognostic value in patients with NK/T cell lymphoma. Oncology Reports, 32, 853-859. https://doi.org/10.3892/or.2014.3237
MLA
Li, Y., Zhang, X., Hu, T., Han, L., Li, R., Wen, J., Zhang, M."Asparagine synthetase expression and its potential prognostic value in patients with NK/T cell lymphoma". Oncology Reports 32.2 (2014): 853-859.
Chicago
Li, Y., Zhang, X., Hu, T., Han, L., Li, R., Wen, J., Zhang, M."Asparagine synthetase expression and its potential prognostic value in patients with NK/T cell lymphoma". Oncology Reports 32, no. 2 (2014): 853-859. https://doi.org/10.3892/or.2014.3237