Correlation Analysis Of IL-34 And CSF-1 With Hepatocellular Carcinoma Family Aggregation In Guangxi

Objective To analyze the expression levels of interleukin-34（IL-34）and colony-stimulating factor-1（CSF-1）in peripheral blood of members from hepatocellular carcinoma（HCC）high-incidence families and cancer-free families in Guangxi.And to study the effect of IL-34 and CSF-1 expression levels on the HCC familial aggregation in Guangxi.Methods A total of 110 cancer-free members from families with a high incidence of HCC were collected from people with a high incidence of HCC in Guangxi（no less than 2 HCC patients were found in their direct blood relatives）.And the similar living background,HBs Ag carrying status,ethnicity,gender,age±5 years apart,and no blood relationship with the high-risk population were selected as the matching conditions.110 members of the cancer-free family（no known history of cancer was found in their linear blood relatives）were selected as the cancer-free family member group.There were 61 male members and 49female members in the HCC high-incidence family group.At the age level,HCC high incidence group,whose members of age range were 2～78 years old,including 61 members age less than or equal to 25-year-old,49 members older than 25-year-old.In terms of ethnic composition,there are 73 Zhuang members and 37 Yao members.In HBs Ag carrying status level,21 HBs Ag positive members and 89 HBs Ag negative members were found in the HCC high-incidence family group.The members of the HCC high-incidence group included48 relatives with a correlation coefficient of 1/2,26 relatives with a correlation coefficient of 1/4,and 36 relatives with a correlation coefficient of 1/8 or above.Among the members with a high incidence of HCC,39 members came from families with a high incidence of HCC in which 2～3 HCC patients had occurred,and 71 members came from families with a high incidence of HCC in which 4 or more patients had occurred.Enzyme-linked immunosorbent assay（ELISA）was used to detect the expression levels of IL-34 and CSF-1.In the statistical analysis,due to the asymmetry of frequency distribution of experimental data in this study,median and quantile spacing methods[M(P₂₅,P₇₅)]are proposed to describe the data.Comparison of measurement data between paired sample groups was performed by Wilcoxon signed-rank test of two correlated samples.Measurement data were compared between unpaired sample groups using two independent samples Mann-Whitney U test.Kruskal-Wallis H nonparametric test of multiple independent samples was used to compare the measurement data among multiple independent sample groups.Results 1.The expression level of IL-34 in peripheral blood serum:The overall expression level of IL-34 was 247.514（161.298,433.465）ng/L in the high-incidence family group and 210.293（116.912,267.805）ng/L in the cancer-free family group,respectively.The overall expression level of IL-34 in the high-wealth family group was significantly higher than that in the cancer-free family group（Z=-3.850,P=0.000）.The expression level of IL-34 in male members of the high-incidence family group and male members of the cancer-free family group were 270.569（143.231,441.012）ng/L and 196.396（182.952,424.131）ng/L,respectively.The expression level of IL-34 in male members of the high-incidence family group was significantly higher than that in male members of the cancer-free family group,and the difference was statistically significant（Z=-2.554,P=0.011）.The expression level of IL-34 was 242.760（182.952,424.131）ng/L and211.317（159.547,263.309）ng/L in the female members of the high-incidence family group and the female members of the cancer-free family group,respectively.The expression level of IL-34 in female members of the high-incidence family group was significantly higher than that in female members of the cancer-free family group,and the difference was statistically significant（Z=-2.944,P=0.003）.The expression level of IL-34 was 242.760（160.682,377.637）ng/L and 222.210（137.371,278.656）ng/L in the less than or equal to 25-year-old members from the high-incidence family group and the less than or equal to 25-year-old members from the cancer-free family group,respectively.In the less than or equal to 25-year-old members the expression level of IL-34 in the high-incidence family group was significantly higher than that in the cancer-free family group,the difference was statistically significant（Z=-2.279,P=0.023）.In the over25-year-old members,the expression level of IL-34 were253.433（156.360,651.486）ng/L and 168.199（103.637,236.250）ng/L,respectively,in the high-incidence family group and cancer-free family group.The expression level of IL-34 in the over 25-year-old members of the high-incidence family group was significantly higher than that of the over the 25-year-old members of the cancer-free family group,with statistical significance（Z=-3.178,P=0.001）.The expression level of Zhuang members of IL-34 was265.096（134.876,651.486）ng/L in the high-incidence family group and171.260（115.556,261.523）ng/L in the cancer-free family group,respectively.The expression level of IL-34 in the Zhuang members of the high-incidence family group was significantly higher than that in the members of the cancer-free family group,and the difference was statistically significant（Z=-4.074,P=0.000）.IL-34expression levels of Yao members in the high-incidence family group and Yao members in the cancer-free family group were 232.038（196.271,327.055）ng/L and 228.439（197.678,275.529）ng/L,respectively.There was no significant difference in the expression level of IL-34 between the Yao members of the high-incidence family group and the Yao members of the cancer-free family group（Z=-0.747,P=0.455）.The expression levels of IL-34 in HBs Ag positive and cancer-free family members were 145.768（106.242,251.510）ng/L and140.012（115.969,183.579）ng/L,respectively.There was no significant difference in the expression level of IL-34 between HBs Ag positive members in the high-incidence family group and HBs Ag positive members in the cancer-free family group（Z=-0.478,P=0.709）.The expression levels of IL-34 in HBs Ag negative and cancer-free families were 270.569（202.121,565.745）ng/L and223.997（120.637,288.316）ng/L,respectively.The expression level of IL-34 in HBs Ag negative members of high incidence family group was significantly higher than that in HBs Ag negative members of the cancer-free family group,with statistical significance（Z=-3.757,P=0.000）.2.Spearman correlation analysis was used to analyze the correlation between the expression level of IL-34 and CSF-1 in peripheral blood of the subjects in the overall study,the members of the high-wealth family group and the members of the cancer-free family group,and the results showed a significant positive correlation（r=0.377,P=0.000、r=0.407,P=0.000、r=0.208,P=0.029）.3.The expression level of CSF-1 in peripheral blood:there was no statistical significance in the overall expression level of CSF-1 in the high-incidence family group compared with that in the cancer-free family group（P>0.05）.Further stratified analysis of CSF-1 showed that the correlation between male members,female members,members less than or equal to 25-year-old,members over 25-year-old,Zhuang members,Yao members,HBs Ag positive members,HBs Ag negative members,and male members,f female members,members less than or equal to 25-year-old,members over 25-year-old,Zhuang members,Yao members,HBs Ag positive members,HBs Ag negative members in the high-incidence family group and the cancer-free family group were observed.There was no significant difference in the expression level of CSF-1（P>0.05）.4.There was no significant difference in the expression level of IL-34 and CSF-1 in the high incidence family member group compared with the relative members with the relative correlation coefficient of 1/2,the relative members with the relative correlation coefficient of 1/4,and the relative members with the relative correlation coefficient of 1/8 or above of the protestors of HCC（P>0.05）.5.There was no significant difference in IL-34 expression level and CSF-1expression level between the members from families with 2～3 probs and those from families with 4 or more probs in the high-wealth family group（P>0.05）.6.In the overall study subjects,the expression levels of IL-34 and CSF-1 in the HBs Ag positive group and HBs Ag negative group were 142.246（112.988,224.594）ng/L,244.100（178.905,509.420）ng/L,and 611.821（391.256,922.249）ng/L,1871.408（1460.526,2806.185）ng/L The expression levels of IL-34 and CSF-1 in HBs Ag positive group were significantly lower than those in HBs Ag negative group,the difference was statistically significant（Z=4.441,P=0.000）.Conclusions:1.The high level of IL-34 expression may have a certain correlation with the HCC family aggregation in Guangxi.2.The expression level of CSF-1 may not be significantly correlated with the HCC family aggregation in Guangxi.3.There may be no synergistic effect between HBV infection and IL-34 and CSF-1 expression levels in HCC family aggregation in Guangxi.