| Background:Hepatoblastoma is a common malignant solid tumor in children.Surgical resection of tumor is the core of the treatment.Cisplatin-based chemotherapy improves the resectability of the tumor and increases the 5-year survival rate to80%.With the development of pediatric surgery,the understanding of the disease is getting deeper and deeper.The prognosis of hepatoblastoma varies greatly among different children.In recent years,more and more scholars have studied prognosis-related indicators of hepatoblastoma.Alpha-fetoprotein(AFP)is the most powerful biomarker for the diagnosis of HB.Its persistent or repeated elevation is a sensitive marker of malignant diseases.But very low alpha-fetoprotein levels are associated with anaplastic histology and adverse outcomes.In pathological types,small cell undifferentiated hepatoblastoma is associated with invasion and poor prognosis.The high expression of?-catenin,cyclinD1 and Ki-67 is a predictor of poor prognosis,but is only occasionally used to support more aggressive treatment.There are few molecular map studies to clarify the molecular mechanism of HB development and identify related potential targets for chemotherapy.In addition,genomic studies have pointed out the key role of Wnt/?-catenin signaling pathway in HB.About 80%of HB have gene mutations that encode?-catenin.There is evidence that crosstalk between Wnt/?-catenin and myc signaling pathways can improve tumor invasiveness.These studies have enhanced the role of Wnt/?-catenin signaling pathway in the treatment of HB.However,no effective method has been found to suppress?-catenin.There is an urgent need to identify the indicators of high-risk HB and find new treatment approaches.In recent years,more and more studies have shown that inflammatory reaction plays an important role in the occurrence and development of tumors.Many systemic inflammatory markers,such as neutrophil lymphocyte ratio(NLR)and platelet lymphocyte ratio(PLR),are considered to be simple and reliable indicators of systemic inflammatory response.They are easily obtained from the blood routine of cancer patients and have proven to be prognostic indicators of multiple cancers(DFS and OS),such as lung cancer,gastric cancer,colorectal cancer,pancreatic cancer,ovarian cancer and endometrial cancer).High NLR was considered as an independent prognostic indicator of poor prognosis before treatment.The patients with high NLR and PLR had higher stages and poor histological types.The changes of NLR and PLR indicate the balance between neutrophil and platelet dependent inflammatory response and lymphocyte mediated anti tumor immune response.The increase of NLR,PLR suggests that the balance is broken,the balance is tilted toward the direction of inflammation,and the anti-tumor immune response is weakened.Objective:To evaluate the prognostic value of of NLR and PLR in patients with hepatoblastoma.Methods:The data of 72 cases of hepatoblastoma treated in our hospital from 2011.1 to2015.12 were analyzed retrospectively.64 cases of hepatoblastomas which met the inclusion criteria were screened out.Blood samples were collected from all children before intervention and the results of peripheral blood were recorded including neutrophil lymphocyte and monocyte count.The values of NLR and PLR were calculated.All the pathological specimens were examined by immunohistochemistry to identify the specific pathological types.PRETEXT staging system was used for tumor staging.The NLR,PLR receiver operating characteristic(ROC)curve was plotted and the cut-off value of the best NLR,PLR was selected by the highest Jordan index.The cut-off value of the best NLR,PLR is selected by the highest Jordan index.The survival curve was completed by Kaplan-Meier and Log-rank test was used to calculate the effect of NLR,PLR on the overall survival rate(OS)and disease-free survival rate(DFS).Univariate analysis was performed with Log-rank method.The significant variables of univariate analysis were included in COX regression to determine the factors that had independent influence on prognosis.Results:1.The neutrophil count,platelet count and NLR,PLR in the case group were significantly higher than those in the healthy control group(t=5.048,P<0.01;t=7.917,P<0.01;t=4.058,P<0.01;t=5.092,P<0.01).There was no significant difference in lymphocyte count between the two groups(t=0.385,P>0.05).2.The analysis of R 0C curve shows that the critical value of NLR is 98.27.The critical value of R0C is 98.27 of 1.04.PLR.NLR<1.04 was defined as low NLR group and NLR?1.04 was defined as high NLR group.PLR<98.27 was defined as low PLR group and PLR?98.27 was defined as high PLR group.3.The difference of NLR in different age groups was statistically significant(?~2=11.807,P=0.008).There was significant difference in NLR between different tumor diameters(?~2=8.332,P=0.018).The larger the diameter,the higher the PLR.The differences of NLR and PLR in different PRETEX stages were statistically significant(?~2=22.490,P=0.000)?(?~2=16.961,P=0.001).NLR and PLR were higher in the patients with higher staging.The difference of NLR,PLR between different pathological types was statistically significant(?~2=10.767,P=0.029)?(?~2=11.690,P=0.020).The NLR and PLR of fetal type were lower.There was no significant difference in NLR and PLR between genders,portal tumor thrombus,tumor number and preoperative AFP.4.The 3-year survival rate of low NLR group was 96.6 and the median survival time was 29.0 months.The 3-year survival rate of high NLR group was 79.4 and the median survival time was 17.0 months.The difference between the two groups was statistically significant(?~2=11.755,P=0.001).The 3-year survival rate in low PLR group was 91.3 months,and the median survival time was 24.5 months.The 3-year survival rate of high PLR group was 85.0 and the average survival time was 17.0months.There was no significant difference in survival between the two groups(?~2=2.091,P=0.148).The 3-year disease-free survival rate of low NLR group was 93.3 and the median survival time was 23.5 months.The 3-year disease-free survival rate of high NLR group was 58.8%and the median survival time was 24.5months.Thedifferencebetweenthetwogroupswasstatistically significant(?~2=15.500,P=0.000).The 3-year disease-free survival rate of low PLR group was 87.5 and the median survival time was 20.5 months.The 3-year disease-free survival rate of high PLR group was 60.0 and the median survival time was 26.0 months.The difference between the two groups was statistically significant(?~2=5.091,P=0.024).The results of univariate analysis using Log-rank showed that the number of tumors(?~2=10.489,P=0.001),PRETEXT preoperative staging(?~2=17.226,P=0.001),pathological classification(?~2=10.489,PP=0.001),preoperative NLR(?~2=11.755,P=0.001)are factors affecting the survival of children.Integrat the significant variables of univariate Analysis into COX regression.Further typing showed that small cell undifferentiated type(HR 3.451,P=0.022)was an independent risk factor for overall survival.The relative risk of small cell undifferentiated type was 3.451 times higher than that of non-small cell undifferentiated type.Single tumor(HR 0.223,P=0.028)?NLR<1.04(HR0.428,P=0.428)is an independent protective factor for overall survival rate.The relative risk of single tumor was 0.223 times higher than that of multiple tumor,and the relative risk of NLR<1.04 was 0.428 times that of NLR?1.04.Conclusion:1.The prognosis of hepatoblastoma in children is related to many factors.Univariate analysis showed that the number of tumors,preoperative stage of PRETEXT,pathological classification and preoperative NLR were the factors influencing the survival of children.The relative risk of small cell undifferentiated type is 3.451 times higher than that of non-small cell undifferentiated type.2.Further multivariate analysis showed that undifferentiated small cell type(HR 3.451,P=0.022)was an independent risk factor for overall survival.Single tumor(HR 0.223,P=0.028),NLR<1.04(HR 0.428,P=0.428)is an independent protective factor for overall survival.The relative risk of single tumor was 0.223 times higher than that of multiple tumors,and the relative risk of NLR<1.04 was 0.428times higher than that of NLR?1.04. |
PDF Full Text Request