| ObjectiveThe expression level of miR-375 in serum of healthy control group,chronic hepatitis B,hepatitis B cirrhosis and HBV-related hepatocellular carcinoma were detected,besides,the correlation between miR-375 and clinical characteristics and laboratory indexes of each group was analyzed.Besides,to explore the relationship between miR-375 and prognosis of HBV-HCC patients and its value in prognosis evaluation.Methods1.Correlation research:From august 2018 to october 2019,in patients with HBsAg-positive HCC and patients with HBV-related diseases were collected as case group in the hepatobiliary center of Wuwei Medical Science Academy of Gansu Province,and healthy control after physical examination(HBsAg negative)enrolled from outpatient department.Then,questionnaire survey and auxiliary examination were carried out and were collected.Serum miR-375was detected by using qRT-PCR.2.Prognosis research:The patients with HBV-DNA high replication that the replication amount>10~5 IU/ml,and the patients with abnormal ALT and AST of liver function were selected as the study objects.The Bio-Plex-Pro human kit was used to detect the cytokine in the Bio plex liquid-phase chip detection system according to the instructions of the kit.By drawing the standard curve,the content of 24 kinds of cytokines in human serum was quantitatively detected.In addition,36 patients who received TACE treatment in the first part of HBV-HCC patients were followed up for one year to analyze short-term survival.3.Statistical analysis:www.equry.cn was used to design questionnaire and collect data,the statistical analyses were carried out with SPSS19.0.Differences between experimental groups were statistically evaluated using Student's t test,ANOVA analysis and Kruskal-Wallis H test.The chi-square test was used to analyze categorical data.Pearson correlation and Spearman rank correlation were used in correlation analysis.Kaplan Meier method was used for prognosis analysis,and ROC was used to evaluate the prognosis of patients with HBV-HCC.P?0.05 was considered to be statistically significant.Results1.Correlation research:(1)348 subjects were enrolled in this study,including 83 healthy controls,110 patients with chronic hepatitis B,100 patients with hepatitis B cirrhosis and 55patients with HBV-HCC.Comparison of general clinical data of four groups:there was no significant difference in sex,age,vaccination and history of drinking among the four groups(P>0.05),and there was significant difference in other biochemical indexes(P<0.05).(2)Expression of miR-375 in HBV related diseases:with the progression of HBV related diseases,the expression level of miR-375 in serum decreased in turn,healthy control group>chronic hepatitis B>hepatitis B cirrhosis>HBV-HCC.(3)The results showed that the expression level of miR-375 in chronic hepatitis B group was negatively correlated with abdominal color Doppler ultrasound,HBV-DNA,HBeAg and HBeAb;the expression level of miR-375 in liver cirrhosis group was negatively correlated with abdominal color Doppler ultrasound,HBV-DNA and gender,but positively correlated with vaccination history;the expression level of miR-375 in HBV-HCC group was negatively correlated with abdominal color Doppler ultrasound,HBV-DNA,HBcAb,ALT and AST were all negatively correlated.(P<0.05).(4)The relationship between miR-375 expression level and parameters of HBV-HCC patients:The expression of miR-375 was negatively correlated with tumor thrombus,tumor number,FibroScan,CEA and AFP(P<0.05).(5)The results of multivariate analysis of linear regression model showed that there was a regression relationship between B-ultrasound,ALT,HBeAg,AFP,FibroScan and the expression level of miR-375 in serum.That is to say,the expression level of miR-375 in patients with negative B-ultrasound,ALT,HBeAg,AFP and FibroScan was higher than that in patients with positive.2.Prognosis research:(1)The expression of cytokines in different groups:APRIL/TNFSF13,IFN-g,IL-6Ra,IL-8,IL-12(p40),IL-27(p28),IL-32,MMP-1,MMP-2,MMP-3,Osteocalcin,TNF-R1,TNF-R2 and TWEAK/TNFSF12 were significant differences.Among them,chitinase 3-like 1,IFN-g,IL-8,IL-6Ra,MMP-1,MMP-2,MMP-3,osteocalin were expressed at the highest level in the healthy control group,and then decreased in turn in chronic hepatitis B,liver cirrhosis and HBV-HCC.However,April/TNFSF13 and TNF-R1,TNF-R2,TWEAK/TNFSF12 have the highest expression level in HBV-HCC.(2)The results of correlation between the expression level of cytokine and miR-375:IFN-g,IL-6Ra,IL-8,IL-12(P40),IL-27(P28),IL-32,MMP-1,MMP-2,MMP-3,osteocalcin were positively correlated with the expression level of miR-375,April/TNFSF13 and TNF-R1,TNF-R2,TWEAK/TNFSF12 were negatively correlated with the expression level of miR-375.(3)The short-term prognosis of patients with HBV-HCC:The prognosis was good in 15 cases and poor in 21 cases.The 1-year survival rate of HBV-HCC was 72.22%,and 41.66%in the group without poor prognosis.The results of Kaplan Meier survival curve showed that the survival time of patients without poor prognosis was 5-18 months,and the median survival time was12 months.(4)The outcome of the two groups was as follows:the expression of miR-375 in the poor prognosis group was lower than that in the good prognosis group.In addition,FibroScan,AFP,ALT in the good prognosis group were significantly higher than that in the poor prognosis group.(5)ROC curve was used to detect miR-375 in evaluating the prognosis of HBV-HCC:The AUC of 21 patients with poor prognosis detected by miR-375 was 0.813,the sensitivity was 84.0%,and the specificity was 73.7%;the AUC of AFP and FibroScan were 0.753 and 0.692,respectively.However,the combined detection of serum miR-375,FibroScan and AFP was used to evaluate the prognosis of HBV-HCC.It was found that the combined prediction of AUC of three indicators was 0.848,and the sensitivity and specificity were higher than that of single indicator,92.1%and 77.2%,respectively.Conclusions1.The expression level of miR-375 in serum decreased with the progression of HBV related diseases,suggesting that the high expression of miR-375 may play a protective role in HCC.2.The expression of serum miR-375was closely related to the clinical characteristics and pathological parameters of patients,suggesting that miR-375 can be combined with other indicators of patients as a marker for the progress of HBV-related diseases,which provides an important clue for the prediction of disease progress and prognosis.3.The level of cytokines in human serum was closely related to the expression of miR-375,indicating that there was a network of mutual regulation between miRNA and cytokines,suggesting that miR-375 combined with a variety of cytokines had a certain practical value in the early diagnosis and prognosis of HBV infection.4.miR-375 was an important serum marker affecting the prognosis of HCC patients,which can be used as a prognostic indicator.5.The combined detection of miR-375,AFP and FibroScan was helpful to evaluate the prognosis of HBV-HCC. |
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