| ObjectiveTo investigate the expression of HSP90AA1/HSPA8 in hepatocellular carcinoma patients with with depression,and analyze its clinical significance and influence on the prognosis of such patients.MethodsPatients with hepatocellular carcinoma who were hospitalized for the first time in the Affiliated Tumor Hospital of Guangxi Medical University from September 2015 to March 2017(without any drugs or invasive treatment)and who had not received surgical treatment for serious heart,brain,lung,kidney,infectious diseases and other diseases were selected.Patients were assessed using self-rating depression scale(SDS)and hospital anxiety and depression scale(HADS)before surgery.Patients were divided into groups as no depression(n=45),mild depression(n=38)and moderate-to-severe depression(n=48).The expression of HSP90AA1/HSPA8 and VEGF/VEGFR2-PI3K-AKT pathway in tumor tissues of the three groups was detected by real-time PCR,immunoblotting and immunohistochemistry.Disease-free survival of the three groups were compared.Results1.In this study,a total of 131 patients with hepatocellular carcinoma who underwent radical hepatectomy were included.The depression score of the patients using HADS-D combined with SDS two scales was assessed.The number of patients without depression was 45.There were 86(65.6%)patients with depression.According to the degree of depression,there were 38(29.01%)patientswithmilddepressionand48(36.64%).patientswith moderate-to-severe depression.Compared with general data of patients,AST of patients with moderate to severe depression,those without depression and those with mild depression had statistical significance(all P<0.05),SDS index score and HADS-D score were both statistically significant(P<0.001).There were no significant differences in other clinical and pathological characteristics(all P>0.05).2.The follow-up date was March 2019.Tumor recurrence occurred in 67patients(51.1%)within 24 months after hepatectomy,including 20 patients(44.4%)in the no depression group,18 patients(47.3%)in the mild depression group,and 29 patients(60.4%)in the moderate-to-severe depression group.The median disease-free survival of all patients included was 10 months,65.3%at 6months,47.3%at 12 months and 36.7%at 24 months.The disease-free survival rate was significantly lower at 6 months(52.8%vs 64.8%vs 65.9%),12months(36.1%vs 50.0%vs 52.1%)and 24 months(28.9%vs 40.1%vs 41.6%)in the moderate-to-severe depression group than in the other two groups(52.8%vs 64.8%vs 65.9%).The median disease-free survival was 8 months in the moderate-to-severe depression group,13 months in the mild depression group,and 14 months in the no depression group.There was no statistically significant difference between the no depression group and the mild depression group(P=0.752).3.Univariate analysis was conducted using age,gender,tumor status,blood biochemical indexes and other variables.The results showed that vascular invasion and moderate-to-severe depression may affect the recurrence of HCC patients(P<0.05).The above factors were included in Cox multivariate regression model analysis.The results showed that vascular invasion and moderate-to-severe depression were factors affecting disease-free survival of HCC patients(P<0.05).4.Real-time quantitative PCR,Western blotting and immunohistochemistry were used to detect HSP90AA1/HSPA8 in the cancer tissues of the three groups ofHCCpatients.Theexpressionofrelatedindicatorsof VEGF/VEGFR2-PI3K-AKT pathway in the cancer tissues of the three groups of HCC patients was detected by Western blotting and Real-time quantitative PCR:(1)Real-time quantitative PCR showed that moderate-to-severe depression group HSPA8 Mrna(4.21?1.17)is significantly higher than mild depression group(3.07±1.69,P<0.001)and the no depression group(2.91±1.73,P<0.001),the relation between the moderate-to-severe depression group HSP90AA1mRNA(5.46±2.31)is significantly higher than the mild depression group(4.29±1.85,P<0.01)and no depression group(3.81±1.64,P<0.001).In addition,there was no statistically significant difference in HSPA8 mRNA and HSP90AA1 mRNA between the mild depression group and the no depression group.(2)Western blotting showed that the average protein level of HSP90AA1in the moderate-to-severe depression group(2.29±0.36)was higher than that in the mild depression group(1.70±0.11,P=0.019)and the no depression group(0.56±0.09,P<0.001),the mean protein levelofHSPA8 in the moderate-to-severe depression group(2.13±0.17)was higher than that in the the mild depression group(1.47±0.16,P=0.009)and theno depression group(0.36±0.10,P<0.001).(3)Immunohistochemical staining showed that the mean protein level of HSPA8 in the mild-to-severe depression group was significantly higher than that in the other two groups(?~2=88.154,P=0.044),the mean protein level of HSP90AA1 was significantly higher than that of the other two groups(?~2=14.334,P=0.006).(4)Western blotting and Real-time quantitative PCR were performed to detect HSP90AA1,HSPA8 and VEGF/VEGFR2-PI3K-AKT1 pathway related proteins and genes in the moderate-to-severe depression group and the non-mild depression group.The results showed that compared with the non-mild depression group,HSP90AA1,HSPA8,VEGF,VEGFR2,PI3K,AKT1 protein and mRNA expression were increased,and Caspase9 and BAD protein and mRNA expression were decreased.The expression of HSP90AA1/HSPA8 may be positively correlated with the expression of VEGF,VEGFR2,PI3K and AKT1,and negatively correlated with the expression of Caspase 9 and BAD.Conclusion1.The incidence of depression in patients with hepatocellular carcinoma is high,and the degrees of depression is various,which should be emphasized.2.Hepatocellular carcinoma patients with moderate to severe depression are more likely to relapse and have poor prognosis,which are independent risk factors affecting their disease free survival.Therefore,evaluation and intervention should be strengthened in hepatocellular carcinoma patients with moderate-to-severe depression.3.HSP90AA1/HSPA8 is highly expressed in hepatocellular carcinoma patients with moderate-to-severe depression,which may be related to the activation of VEGF/VEGFR2-PI3K-AKT pathway.4.The patients with hepatocellular carcinoma who have moderate-severe depression and high expression of HSP90AA1/HSPA8,which should be practiced accurate nursing and provide targeted psychosocial factors intervention,strengthen follow-up,improve patient prognosis and improve quality of life. |
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