title: Asparagine synthetase expression and its potential prognostic value in patients with NK/T cell lymphoma.
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.
authors.affiliation: Lymphoma Diagnosis and Treatment Center, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Lymphoma Diagnosis and Treatment Center, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Lymphoma Diagnosis and Treatment Center, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Tengpeng
authors.initials: T
authors.lastname: Hu
authors.affiliation: Lymphoma Diagnosis and Treatment Center, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Han
authors.affiliation: Lymphoma Diagnosis and Treatment Center, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Ruping
authors.initials: R
authors.lastname: Li
authors.affiliation: The Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wen
authors.affiliation: Lymphoma Diagnosis and Treatment Center, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
mesh_terms: D001217:Aspartate-Ammonia Ligase / Q000235:genetics*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000378:metabolism* / Q000473:pathology; D008223:Lymphoma / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D001217:Aspartate-Ammonia Ligase