Analysis Of Prognostic Factors Associated With Angioimmunoblastic T-cell Lymphoma

Background.Angioimmunoblastic T-cell lymphoma is a subtype of peripheral T-cell lymphoma originating from Follicular Helper Cells.The tumor microenvironment of AITL consists of tumor cells with TFH phenotype infiltrated with multiple immune cells.CHOP and CHOPE are commonly used as first-line treatment options in clinical practice,but the recurrence rate is high and long-term survival is poor.With the intensive research on immunotherapy and gene therapy,immune checkpoint inhibitors and gene targeted therapy have brought hope to many tumor patients,but the prognostic impact of immune checkpoint expression and gene mutation in AITL is unclear.Therefore,studying molecular markers associated with the prognosis of AITL patients is important in improving the prognosis of AITL patients by assessing their prognosis in a timely manner and making the treatment individualized and refined.Objectives.Analysis of programmed cell death receptor 1,programmed cell death 1 ligand 1,B and T lymphocyte attenuator,T cell immunoreceptor with Ig and ITIM domains expression in AITL,and their relationship with clinicopathological features and prognosis;analysis of gene mutations in AITL and their relationship with clinicopathological features and prognosis.Materials and Methods.1.Twenty cases of angioimmunoblastic T-cell lymphoma diagnosed by surgical resection histopathology at the People’s Hospital of Henan University from January 1,2017 to December 31,2021 were collected as the experimental group,and six patients with necrotizing lymphadenopathy were randomly collected as the control group;2.Collection of clinicopathological data,including:gender,age,number of extra-nodal invasion,laboratory findings,pathology reports,etc.,in parallel with IPI score,Ann Arbor staging,ECOG score,etc;3.Apply immunohistochemistry to detect PD-1,PD-L1,BTLA,TIGIT expression in the specimens;apply targeted capture sequencing technology of high-throughput sequencing platform to detect gene mutations in the specimens;4.Apply SPSS 21.0 software to correlation analysis and prognosis analysis of immune checkpoint molecules and gene mutation loci with clinical characteristics,etc.,and plot survival curves.Results.1.The positive rates of PD-1,PD-L1,BTLA,and TIGIT in AITL were 65%(13/20),55%(11/20),30%(6/20),and 60%(12/20),respectively,and the positive expression of PD-1 in AITL was significantly higher than that in necrotizing lymphadenitis,which was statistically significant(P=0.015).2.Among the 20 AITL patients,serum LDH levels were higher in AITL patients with positive PD-1 expression,and the difference was statistically significant(P=0.007);platelet levels were lower in AITL patients with positive PD-L1 expression,and the difference was statistically significant(P=0.028);however,the differences between the expression of BTLA and TIGIT and each pathological factor of the patients were not statistically significant(P>0.05).3.In AITL tissue,BTLA showed a moderate positive correlation with PD-1 expression(r=0.480,P=0.032).4.Among 20 AITL patients,a total of 18(90%)AITL specimens were detected with 23 mutations,and the top 4 high-frequency mutated genes were TET2(75%,15/20),DNMT3A(40%,8/20),RHOA(35%,7/20),and IDH2(30%,6/20).The mutation rate of TET2 was significantly higher in AITL than in patients with necrotizing lymphadenitis,and the difference was statistically significant(P=0.018).5.In 20 patients with AITL,the difference between IDH2 mutation status and patient’s leukocyte level was statistically significant(P=0.007).6.In AITL tissues,there was a moderate positive correlation between TET2 and DNMT3A(P=0.036).7.The Kaplan-Meier survival curve analysis showed that patients with ECOG score 0-1,Plt count≥125×109/L,PD-1,PD-L1,BTLA negative expression and RHOA mutant type had longer overall survival(OS)with statistically significant differences,P-values respectively were 0.018,0.044,0.025,0.027,0.034,0.026,;Progression-free survival(PFS)was longer in patients with ECOG score 0-1,PD-1 negative expression,and RHOA mutant type,with statistically significant differences,P-values respectively were 0.048,0.009,and 0.009.8.Multifactorial analysis showed that ECOG score and BTLA were independent risk factors for OS in AITL patients;PD-1 and RHOA were independent risk factors for PFS in patients.Conclusions.1.The positive expression rate of PD-1 was significantly higher in AITL and the mutation rate of TET2 was statistically higher in AITL compared with necrotizing lymphadenitis.2.PD-1,PDL-1,BTLA positive and RHOA wild type are poor prognostic factors in AITL.3.BTLA positivity is an independent poor prognostic factor for OS in AITL patients;PD-1 and RHOA are independent poor prognostic factors for PFS in patients.