Expression Of IRAK1 In Hepatoblastoma Was Associated With The Clinicopathological And Prognosis

ObjectiveInterleukin-1 receptor associated kinase 1(IRAK1),as a down-stream of toll-like receptor(TLR)signaling,plays important roles in series of malignancies tumours.However,the association between the underlying molecular mechanism of IRAK1 and the prognosis of hepatoblastoma(HB)is unclear.We studied whether the protein expression of IRAK1 in hepatoblastoma tissue correlates with tumor progression.Methods and materialsA total of 70 patients with a pathology confirmed diagnosis of hepatoblastoma were treated in the First Affiliated Hospital of Zhengzhou University from August2011 to January 2018 were retrospectively analyzed.Children older than 18 years were excluded from the study.Patient data were analyzed for survival with gender,age at diagnosis,AFP concentration,tumour size,histopathology,PRETEXT stage,COG stage,vascular invasion/metastases,relapse,chemotherapy and other factors.We followed up one to seven years.Pathological specimens made into tissue microarrays.Tissue of 70 cases were tested for IRAK1 expression using immunohistochemistry.The clinicopathological of high expression IRAK1 tumours was determined using the Chi-squared test in SPSS Version 21.Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazards models.Results1.Microarray of hepatoblastoma showed that IRAK1 was negatively expressed in normal liver tissue.The expression of IRAK1in the 70 HB children was different,with high expression accounting for 58.6%(41/70)and low expression 41.4%(29/70).We found that the expression of IRAK1 in PRETEXT III-IV stage was significantly higher compared with that in PRETEXT I-II stage(X~2=4.427,P=0.035).The high expression of IRAK1 in HB tissues was associated with invasive/metastatic tissues(X~2=6.557,P=0.01).There were no significant differences between patients with low and high IRAK1 expression in age,sex,relapse,COG stage,AFP concentration,tumour size,and histopathology.2.COGIII-IVstage(X~2=16.735,P<0.001),vascularinvasion/metastases(X~2=23.436,P<0.001)and PRETEXT III-IV stage(X~2=9.640,P=0.002),relapse(X~2=25.300,P<0.001),Standard risk vs High risk(X~2=11.724,P=0.001)and the high expression of IRAK1(X~2=8.009,P=0.005)were associated with a poorer prognosis in the Log Rank univariate analysis.Gender(X~2=0.523,P=0.469),age(X~2=0.019,P=0.891),Tumor size(X~2=0.128,P=0.720),AFP<100000vs>100000(ng/ml)(X~2=2.838,P=0.092),histopathology(X~2=0.019,P=0.891),preoperative chemotherapy vs the direct surgery group(X~2=0.832,P=0.362)were not associated with prognosis in the Log Rank univariate analysis.3.Kaplan-Meier survival analysis demonstrated that patients with high IRAK1expression(5 year OS of 55.7±8.6%)had shorter OS than those low IRAK1expression(5 year OS of 91.6±5.7%).Relapse have a 5 year OS of20.5±12.0%.Vascular invasion/Metastatic have a 5 year OS of 29.8±13.9%.The high risk group is associated with significantly worse 5YOS(46.1±10.8%)in HB.4.Vascular invasion/metastases(RR:8.610,P=0.003),relapse(RR:3.558,P=0.026),and the high expression IRAK1(RR:8.797,P=0.011)were associated with an adverse prognosis in the Cox multivariable analysis.This study provides preliminary evidence that high IRAK1 expression,vascular invasion,metastases,and relapse correlate with poorer survival in hepatoblastoma.Conclusions1.IRAK1 markedly correlated with aggressive tumor behaviors and contributed to the progression of HB,indicating that IRAK1 expression might serve as a biomarker for tumor progression and that targeting the IRAK1 signaling pathway might improve prognosis of patients with HB.2.The study provides evidence that the high IRAK1 expression level,vascular invasion/metastases,and relapse are an independent risk factor of hepatoblastoma.