The Expression And Significance Of Key Moleculars In Wnt/β-catenin Signal Pathway Of Human NK/T-cell Lymphoma

ObjectiveMalignant Lymphoma is a kind of heterogeneous diseases originates from lymphocytes or their precusor cells which mainly occurrs in lymph nodes or external lymphoid tissues and organs. NK/T cell lymphoma is a subtype of lymphoma which is special in clinical feature,histology,immunology. In Asia especially China,the incidence of NK/T cell lymphoma is higher than the Europe and America.It accounts for about 21.38% of lymphoma.The main clinical manifestations are damaged lesions with external nose,nasal cavity,nose pharynx,jaw and other parts. Sometimes it concomitants with B symptoms,such as fever,emaciation and night sweats.Severe cases can accompany with systemic spread. The progress of the disease is critical and the prognosis is poor. Its pathogenesis is still unclear.In recent years,signaling pathways are hot pots in the pathogenesis of cancers.As a classic signaling pathway,Wnt/β-catenin pathway has been confirmed that related to the occurrence of varietious tumors. The hub molecular β-catenin’s gathered in cytoplasm is regarded as a sign of its activation.Our study ordered to investigate the expression and significance of key moleculars( β-catenin,c-myc and cyclin D1)in Wnt/β-catenin pathway of NK/T cell lymphoma. We aimed to investigate the expression of key moleculars in the Wnt/β-catenin signal pathway in association with the clinicopathological features and prognosis in NK/T-cell lymphoma(NKTCL). Methods50 cases of NKTCL and 20 reactive hyperplasia of lymph node tissues were obtained from the First Affiliated Hospital of Zhengzhou University.Real time quantitative PCR(RQ-PCR), immunocytochemistry and immunohistochemistry SP methods were used to detect both the transcriptional and translational levels of β-catenin,c-myc and cyclin D1 in human NKTCL cell lines(SNK-6 and YTS) and NKTCL tissues.The correlations between the expression and NKTCL clinicopathology features and prognosis were analyzed subsequently. Results1. The transcript levels of β-catenin,c-myc,cyclin D1 were significantly elevated in SNK-6 and YTS cell line in comparison with that in normal NK cells(P<0.05);2. The protein expression levels of β-catenin, c-myc and cyclin D1(24%、56% and 52%)were higher than reactive hyperplasia of lymph node tissues(0%、25% and 10%),P<0.05。The positive expression levels of c-myc and cyclin D1 were positively correlated with β-catenin.3. The high expression of β-catenin, c-myc and cyclin D1 were significantly correlated with III-IV Ann Arbor stage, the high expression of c-myc was also correlated with Ki-67 level. Kaplan–Meier survival analysis revealed that increased expression of β-catenin correlated with poor clinical outcomes of NKTCL patients(23.662±2.768 months VS 31.65±1.780 months, respectively, P=0.023). Conclusion1. The expressions of of β-catenin, c-myc and cyclin D1 are high in NKTCL and are closely correlated with Ann Arbor stage and prognosis of NKTCL.2. The abnormal activation of Wnt/β-catenin signal pathway may has certain effects on the development of NKTCL.