Clinical Application Value And Mechanism Of PP2Ac Protein In Hepatocellular Carcinoma

Objective:Based on the basic and clinical treatment of HCC,the expression of PP2 Ac protein in hepatocellular carcinoma and its involvement in the occurrence and development of hepatocellular carcinoma and its correlation with the prognosis of HCC patients were studied.Methods:Through bioinformatics retrieval,the expression of PP2 Ac protein in HCC and the mechanism of its involvement in the occurrence and development of HCC were studied.To detect the expression of PP2 Ac protein in HCC tissues and analyze its correlation with the clinicopathological data of HCC patients,further investigate the effect of PP2 Ac protein expression difference on postoperative prognosis of HCC patients and establish a Nomogram model to predict postoperative survival rate of HCC patients.Mi RNAs targeted at PP2 Ac were predicted and screened through retrieval through mi RWalk 2.0 website.Results:(1)Bioinformatics analysis showed that the expression level of PP2 Ac protein in HCC tissues was higher than that in adjacent tissues.GO functional annotation and KEGG signal pathway enrichment analysis of PP2 Ac protein coexpression gene showed that the biological process of GO functional annotation was mainly enriched in nuclear fission,organelle fission,nuclear chromosome separation and chromatin separation.The most important KEGG signaling pathway is the drug metabolism-cytochrome P450 pathway;(2)The expression levels of PP2 Ac protein in HCC and paracancer tissues were(3.01±0.47)and(1.25±0.22)respectively by Western Blotting,with statistically significant differences(P < 0.05);Immunohistochemistry showed that the expression of PP2 Ac protein in HCC tissues was higher than that in adjacent tissues,and the difference was statistically significant(P < 0.05);(3)The preoperative IL-2 of patients with high PP2 Ac expression group was significantly decreased(2158.4±674.9)pg/m L than that of patients with low PP2 Ac expression group(3072.6±536.1)pg/m L,and the difference was statistically significant(P<0.05);(4)the m OS of HCC patients with low expression of PP2 Ac was 40 months,and that of HCC patients with high expression of PP2 Ac was 25 months;The m RFS of HCC patients in the low expression group of PP2 Ac protein was 11 months,and that of HCC patients in the high expression group was 8 months,the difference was statistically significant;(5)To construct a Nomogram prediction model based on independent prognostic factors of PP2 Ac protein expression and clinicopathological data,including PP2 Ac protein expression can improve the C-index of the model,and multiple indicators of in-queue evaluation show that this Nomogram prediction model has a good prediction ability;(6)Mi R-200a-3p,Mi R-139-5p,Mi R-141-3p and Mi R-5480-3p are potential mi RNAs that we found targeting PP2 Ac protein.Conclusion:(1)Bioinformatics retrieval results indicated that PP2 Ac protein was highly likely to be a oncogenic factor in HCC;(2)GO annotation of PP2 Ac coexpression gene and KEGG pathway enrichment analysis indicated that PP2 Ac gene may be multifunctional and multipathway involved in the occurrence and development of HCC;(3)PP2Ac coexpression gene PPI network indicates that high expression of PP2 Ac may have adverse effects on the prognosis of HCC;(4)The expression level of PP2 Ac protein in HCC tissues was higher than that in adjacent tissues,suggesting that PP2 Ac protein could be a oncogenic factor;(5)High expression of PP2 Ac protein has an effect on preoperative immune function of HCC patients,and the specific mechanism remains to be studied;(6)Low expression of PP2 Ac protein significantly prolonged OS and RFS in HCC patients,suggesting that high expression of PP2 Ac protein promoted the invasion and metastasis of HCC to a certain extent;(7)This Nomogram risk stratification model can effectively stratify HCC patients,and has good prognostic ability and high accuracy;(8)Low levels of Mi R-200a-3p and Mi R-139-5p may lead to the elevation of PP2 Ac protein,thereby promoting the occurrence of HCC.Objective: In this part,the expression of PP2 Ac protein in hepatocellular carcinoma and its involvement in the occurrence and development of hepatocellular carcinoma were studied through bioinformatics retrieval.Methods: Firstly,whole-genome co-expression genes of PP2 Ac protein in HCC tissues were screened by Pearson correlation coefficient,and these co-expression genes were analyzed by Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to understand the potential mechanism of PP2 Ac protein in HCC;The protein-protein interaction(PPI)network was constructed using the online STRING database(https://string-db.org/)and visualized by Cytoscape software.Results:(1)Bioinformatics analysis results showed that the expression level of PP2 Ac protein in HCC tissues was higher than that in paracancer tissues.The high expression of PP2 Ac protein significantly was correlated with the gender and TNM stage of HCC patients,and the TNM stage of HCC patients with high expression of PP2 Ac protein was late.(2)Through GO functional annotation and KEGG signal pathway enrichment analysis of PP2 Ac protein coexpression gene,the GO functional annotation biological process is mainly enriched in nuclear fission,organelle fission,nuclear chromosome separation and chromatin separation;KEGG signaling pathways identified that the most important one is drug metabolism-cytochrome P450;(3)PPI network further identified CCNA2 gene as the up-regulated central gene of HCC,and CCNA2,AURKB,TOP2 A,NCAPG,MCM2,CDC20,CCMB2,AURKA and MGST1 were the first nine hub genes with high connectivity.Conclusion:(1)Bioinformatics retrieval results indicated that PP2 Ac protein was highly likely to be a oncogenic factor in HCC.(2)GO annotation of PP2 Ac coexpression gene and KEGG pathway enrichment analysis indicated that PP2 Ac gene may be multifunctional and multipathway involved in the occurrence and development of HCC.(3)PP2Ac coexpression gene PPI network indicates that high expression of PP2 Ac may have adverse effects on the prognosis of HCC;(4)PP2Ac protein may be a potential therapeutic target for HCC,and studying the mechanism of action of PP2 Ac protein on HCC has great clinical research value.Objective: The expression of PP2 Ac protein in HCC tissues was detected,and its correlation with clinicopathological data of HCC patients was analyzed.Further study the influence of PP2 Ac protein expression difference in HCC tissues on postoperative prognosis of HCC patients and construct a Nomogram model to predict postoperative survival rate of HCC patients.Methods: In this study,Western blotting and immunohistochemistry were used to detect the expression level of PP2 Ac protein in human HCC tissues and adjacent tissues respectively.According to the results of immumahistochenistry detection of PP2 Ac protein in HCC tissues,HCC patients were divided into high expression group of PP2 Ac protein(medium and strong positive)and low expression group of PP2 Ac protein(negative and weak positive).Forty patients in each group were randomly selected for preoperative detection of IL-2 and IFN-γ levels.Correlation analysis was conducted between PP2 Ac protein expression level and clinicopathological data of HCC patients,and OS and RFS of the two groups were compared to study the influence of PP2 Ac protein expression difference in HCC tissues on postoperative prognosis of HCC patients.Combined with clinicopathological data of HCC patients,independent factors affecting the prognosis of HCC patients were analyzed,and a Nomogram model to predict the postoperative survival rate of HCC patients was constructed and evaluated.Results:(1)Western Blotting detected the expression level of PP2 Ac protein in HCC tissues and adjacent tissues were(3.01±0.47)and(1.25±0.22),respectively.The expression level of PP2 Ac protein in HCC tissues was higher than that in adjacent tissues,and the difference was statistically significant(P <0.05);(2)PP2Ac protein was highly expressed in 88 of the 128 HCC tissues,with a high expression rate of 68.8%.The expression of PP2 Ac protein in HCC tissues and adjacent tissues was significantly different(P< 0.05);(3)The IFN-γ level in the PP2 Ac high expression group was(1472.2±326.8)pg/m L before operation,and that in the PP2 Ac low expression group was(1488.8±393.3)pg/m L before operation,there was no significant difference(P >0.05).However,il-2 in the group with high PP2 Ac expression was significantly decreased(2158.4±674.9)pg/m L compared with the group with low PP2 Ac expression(3072.6±536.1)pg/m L,and the difference was statistically significant(P< 0.05).(4)Univariate Co X analysis of clinicopathological data showed that there were significant differences in BCLC stage,number of tumors,Edmondson grade,liver cirrhosis,MVI,AFP and capsule integrity between the high expression group and the low expression group(ALL P< 0.05).Multivariate Co X analysis showed that intact capsule and cirrhosis were independent prognostic factors in HCC patients(P<0.05).(5)the m OS of HCC patients with low expression of PP2 Ac was 40 months,and that of HCC patients with high expression of PP2 Ac was 25 months;The m RFS of HCC patients in the low expression group of PP2 Ac protein was 11 months,and that of HCC patients in the high expression group was 8 months.(6)To construct a Nomogram prediction model based on independent prognostic factors of PP2 Ac protein expression and clinicopathological data,it is found that including PP2 Ac protein expression can improve the C-index of the model,and multiple indicators evaluated in the study queue show that the model has good predictive ability.Conclusion:(1)The expression level of PP2 Ac protein in HCC tissues was higher than that in adjacent tissues,suggesting that PP2 Ac protein could be a oncogenic factor.(2)High expression of PP2 Ac protein has an effect on preoperative immune function of HCC patients,and the specific mechanism remains to be studied.(3)Low expression of PP2 Ac protein significantly prolonged OS and RFS in HCC patients,suggesting that high expression of PP2 Ac protein promoted the invasion and metastasis of HCC to a certain extent.(4)The Nomogram risk stratification model can effectively stratify HCC patients,and has good prediction ability and high accuracy for HCC patients’ prognosis.Objective: The mi RNAs targeted at PP2 Ac were predicted and screened through retrieval through mi RWalk 2.0 website.Methods: Mi RWalk 2.0 was used to predict mi RNAs that might target PP2 Ac using mi RNA-Seq expression data from public databases and RNA detection data from 20 HCC cancer tissues.Results: Mir-200a-3p,Mir-139-5p,Mir-141-3p and Mir-5480-3p are potential mi RNAs targeting PP2 Ac protein.The expression level of Mir-200a-3p and Mir-139-5p in HCC tissues was lower than that in normal liver tissues,while the expression level of Mir-5480-3p was higher than that in normal liver tissues.There was no significant difference in the expression level of Mir-141-3p between HCC and normal liver tissues.Conclusions: Low levels of Mir-200a-3p and Mir-139-5p may lead to the elevation of PP2 Ac protein,thereby promoting the occurrence of hepatocellular carcinoma.