| Objective:In this paper,protein and mRNA expression levels of CXCL12/CXCR4/CXCR7 were examined in Formalin Fixed Paraffin Embedded tissues of T lymphoblastic lymphoma/leukemia(T-LBL/ALL)and its correlation with clinicopathological features and prognosis were discussed.Methods:First,we collected Formalin Fixed Paraffin Embedded tissues of 72 cases of T-LBL/ALL from 2001 to 2015.All With complete clinicalpathological and outcome records.They were from the department of pathology in Shanxi Cancer Hospital.Meanwhile,30 cases of reactive hyperplasia of lymph node(LH)considered as control group.Second,Using issue microarray,immunohistochemical EnVison method to detect CXCL12,CXCR4,CXCR7,Ki-67 protein and practically diagnostic markers,such as CD3,?CD3,CD99,CD5,CD7,TdT,CD1?,CD43 and CD34 etc.Last but not least,the mRNA relative expressions of CXCL12,CXCR4 and CXCR7 were detected by Real-time RT-PCR method in T-LBL/ALL and LH groups.In addition,we analysed correlation between protein and mRNA expression levels of CXCL12/CXCR4/CXCR7 and clinicopathological features and prognosis by SPSS17.0.Results:1.Expression levels of protein by immunohistochemistry: The positive rates of 72 cases of T-LBL/ALL were CXCL12(84.7%),CXCR4(91.6%)and CXCR7(none),respectively.Positive rates of Ki-67<80% and ?80% were 25 cases(34.7%)and 47 cases(65.3%),respectively.2.Relative expression levels of mRNA by Real-time RT-PCR: Relative expression levels of CXCL12,CXCR4 and CXCR7 mRNA in T-LBL/ALL were 62.4%,71.46% and18.54% respectively,and the difference was statistically significant(P<0.05).3.Single factor risk analysis:In T-LBL/ALL,the expression of CXCL12 mRNA were positively correlated with Ann Arbor stage and KPS score,and the differences were statistically significant(P<0.05).CXCL12 protein were positively correlated with splenomegaly and LDH level,and the differences were statistically significant(P<0.05).Related expression level of CXCR4 mRNA was positively correlated with IPI score,clinical symptoms,mediastinal invasion,,and bone marrow infiltration,and the differences were statistically significant(P<0.05).CXCR4 protein was positively correlated with mediastinal invasion,and the difference was statistically significant(P<0.05).Related expression level of CXCR7 mRNA were positively correlated with clinical symptoms,mediastinal invasion,extranodal recidivism and bone marrow infiltration,and the differences were statistically significant(P<0.05).In addition,the expression of CXCL12 mRNA and CXCL12 protein and CXCR4 protein expression were positively correlated(P<0.05),but there was no correlation between others(P>0.05).4.Multivariate COX regression analysis : High expression of CXCR4 protein,hepatosplenomegaly and bone marrow infiltration were risk factors affected the prognosis of T-LBL /ALL.Conclusion:The expressions of CXCL12/CXCR4/CXCR7 were correlated with mediastinal invasion,lymph node and bone marrow infiltration,clinical symptoms of B and other factors in T-LBL/ALL,suggesting that the chemokine axis CXCL12/CXCR4/CXCR7 plays an essential role in the occurrence and development of T-LBL/ALL.In addition,the protein expressions of CXCL12,CXCR4 and CXCR7 are not fully reflected by the transcription levels of CXCL12,CXCR4 and CXCR7.In the occurrence and development of T-LBL/ALL,they were not only diifferent from normal issues in mRNA transcription levels and protein expressions,they also may regulate different signaling pathways that affect the progress of T-LBL/ALL.The complexity of the interaction mechanism of CXCL12,CXCR4 and CXCR7 needs further study.With the continuous development and clinical trials of CXCR4 and CXCR7 antagonists,it is worth looking forward to a promising strategy for treating T-LBL/ALL by antagonizing the CXCL12/CXCR4/CXCR7 axis. |
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