Expression And Significance Of CDK6 And FOXM1 In Peripheral T Cell Lymphoma

Objective:Bioinformatics analysis combined with experimental verification methods was used to study the expression of CDK6 and FOXM1 in peripheral T-cell lymphoma(PTCL)and reactive hyperplasia of lymph nodes.Analysis: 1)Correlation between the expression of CDK6,FOXM1 and the clinicopathological parameters and prognosis of patients with PTCL;2)Correlation between the expression of CDK6,FOXM1 protein and relative mRNA expression in PTCL;3)Correlation between the expression of CDK6 and FOXM1 in PTCL.We hope to provide new ideas for the early diagnosis,clinical treatment and patient prognosis of PTCL.Methods:1.Oncomine 4.5 database was used to analyze the expression levels of CDK6 and FOXM1 mRNA in PTCL tissues.2.A total of 166 paraffin specimens were collected from patients diagnosed with PTCL in the Department of Pathology of Shanxi Cancer Hospital from January 2006 to December 2018.A total of 166 patients(including a total of 130 PTCL patients with a complete clinical course record and a total of 100 specimens with sufficient paraffin cancer tissue)were set as the experimental group;30 cases of lymph node reactive hyperplasia archive paraffin samples were randomly selected as the control group,and tissue chips were made separately.3.Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of CDK6 and FOXM1 mRNA in 100 cases of PTCL paraffin cancer tissues and 30 cases of lymph node reactive hyperplasia paraffin specimens,and the relationship between the mRNA expression and protein expression was analyzed.The correlation between each index and clinicopathological parameters of the patients with PTCL was analyzed.4.Immunohistochemical method(En Vision)was used to detect the protein expression of CDK6 and FOXM1 in 166 cases of PTCL and 30 cases of lymph node reactive hyperplasia paraffin,and the correlation between the protein expression of CDK6 and FOXM1 was analyzed.The correlation between each index and clinicopathological parameters and prognosis of the patients with PTCL was analyzed.Results:1.Bioinformatics analysis results: Data in the Oncomine 4.5 database showed that mRNA expression of CDK6 and FOXM1 in PTCL tissues are significantly higher than in normal tissue(P<0.05).2.qRT-PCR results: The relative expression of CDK6 mRNA in the tissues of 100 PTCL patients was 0.546(0.487,0.645),which was significantly higher than that of lymph node reactive hyperplasia tissue 0.167(0.107,0.233)(P<0.05);The relative expression of FOXM1 mRNA was 1.755(0.939,1.915),which was also significantly higher than that of lymph node reactive hyperplasia tissue 0.847(0.729,0.947)(P<0.05).3.Immunohistochemical results: CDK6 protein was mainly expressed in tumor cell nucleus and cytoplasm in 166 cases of PTCL paraffin,with a positive rate of 27.7%(46/166),and 30 cases of lymph node reactive hyperplasia paraffin tissue were mainly expressed in lymphatic follicular germinal center.T-zone cells are not expressed;FOXM1 protein was also mainly expressed in the tumor cell nucleus and cytoplasm in 166 cases of PTCL paraffin,with a positive rate of 80.7%(134/166).Outside the germinal center of lymphoid follicles,some T-zone cells were also expressed,with a positive rate of 30%.4.Correlation between CDK6,FOXM1 protein expression and their mRNA expression: The relative expression of CDK6 mRNA and its protein expression in PTCL tissues are not related(P>0.05);the relative expression of FOXM1 mRNA and its protein expression are also unrelated(P>0.05).5.The relationship between CDK6,FOXM1 and clinicopathological characteristics of PTCL patients: The expressions of CDK6 and FOXM1 mRNA in PTCL tissues were not related to the clinicopathological characteristics of patients(P>0.05).The expressions of CDK6 and FOXM1 proteins and their co-expression in PTCL tissues were positively correlated with the patient's Ann Arbor stage and International Prognostic Index(IPI)score(P<0.05).6.The relationship between the expression of CDK6,FOXM1 protein and clinicopathological features and the prognosis of patients with PTCL: In the group with high expression of CDK6,the survival time of patients was shorter than that of the group with low expression of CDK6(P?0.05);In the group with high expression of FOXM1,the survival time of patients was shorter than that of the group with low expression of FOXM1(P?0.05).There was no significant correlation between clinicopathological features and prognosis in patients with PTCL(P>0.05).7.Correlation between co-expression of CDK6 protein and FOXM1 protein and clinicopathological parameters and prognosis: Spearman correlation analysis showed that CDK6 protein expression in PTCL tissues was positively correlated with FOXM1 protein expression(r=0.200,P?0.05).The co-expression of CDK6 protein and FOXM1 protein group was related to the Ann Arbor stage and IPI score of the patients,and was not related to the patient's gender,age,LDH level,and B symptoms.And the co-expression of CDK6 protein and FOXM1 protein group had lower overall survival than the other groups(P?0.05).Conclusion:1.Through the method of bioinformatics analysis,there is a certain predictive guidance for the expression level of the genes(CDK6,FOXM1)studied in this subject in PTCL.2.The expression of mRNA and protein of CDK6 and FOXM1 in PTCL tissue and reactive proliferative lymph node tissue are different,which may be new targets for diagnosis and treatment of PTCL.3.The expression of CDK6 and FOXM1 proteins and their co-expression were positively correlated with the patient's Ann Arbor stage and IPI score.Moreover,patients with PTCL with high expression of CDK6 and FOXM1 have shorter overall survival,suggesting that CDK6 and FOXM1 may be involved in the occurrence and development of PTCL,affecting their prognosis.4.The overexpression of CDK6 may lead to the enhanced function of transcription factor FOXM1,and the overexpression of CDK6 and FOXM1 as an adverse factor promotes the occurrence and development of PTCL.