Expression And Clinical Significance Of Lipase Member-H（LIPH） In Pancreatic Cancer

Background:Pancreatic cancer（PC）is one of a growing global burden of malignant tumors.Compared with other malignancies,pancreatic cancer has a lower incidence but a lower survival rate.Pancreatic cancer has insidious onset,rapid progression and early metastasis.Currently,pancreatic cancer is treated with surgery and chemotherapy,most patients have already missed surgery by the time they are diagnosed.At present,the treatment effect and prognosis of pancreatic cancer are very poor.Unresectable pancreatic cancer is mainly treated with chemotherapy,supplemented by local treatment to improve symptoms.In view of the current treatment status of pancreatic cancer,the pathogenesis and treatment of pancreatic cancer need to be further studied.Objective:To explore the expression difference of LIPH in pancreatic and paracancer pancreatic tissues and its correlation with clinicopathological features and prognosis of patients with pancreatic cancer,so as to provide basis for diagnosis and treatment of pancreatic cancer and improvement of prognosis.Methods:1.（1）Based on bioinformatics methods,the expression of LIPH in pancreatic cancer and its correlation with clinical prognosis were analyzed in TCGA database and GEPIA database;（2）The biological function of LIPH gene enrichment was analyzed by R language;（3）Methylation of LIPH gene in pancreatic cancer was detected in TCGA database,and other genes interacting with LIPH gene were analyzed in Gene MANIA database.2.q-PCR was used to analyze the expression of LIPHm RNA in different pancreatic cancer cell lines.3.Pancreatic cancer tissue microarray was used,project number:Hpan A180Su03.The number of samples was 90 cases of pancreatic cancer during survival and 90 cases of paracancer,including basic clinical data such as survival time.Immunohistochemistry was used to investigate the correlation between LIPH gene expression and clinicopathological data and prognosis of pancreatic cancer.Results:1.（1）Survival curves of LIPH expression and prognosis in pancreatic cancer were analyzed based on GEPIA database and TCGA database,and it was found that patients with high LIPH expression had poor prognosis（P=0.048）;（2）KEGG pathway enrichment analysis and GO enrichment analysis were performed by R language,and LIPH was found to be closely related to protein processing,transportation,hydrolysis,viral infection,nuclear cytoplasmic transport,Golgi vesicle transport,nucleic acid transport,RNA transport and other biological processes;（3）The methylation level of LIPH gene promoter in pancreatic cancer was significantly lower than that in normal pancreatic tissue（P<0.05）.Single-gene PPI prediction revealed that LIPH interacted with LIPI,LIPG,LIPC,LPL,PNLIPRP and other lipase members.2.q-PCR results showed that the expression of LIPHm RNA in four pancreatic cancer cell lines（As PC-1,PANC-1,SW1990,CFPAC-1）was significantly higher than that in normal pancreatic cancer cell lines（h HERT-HPNE）（P<0.05）.3.Immunohistochemical results showed that LIPH is not only highly expressed in pancreatic cancer,but also mainly expressed in pancreatic cancer cytoplasm.LIPH expression was associated with the degree of differentiation,distant metastasis and preoperative CA19-9 level.Univariate COX regression analysis showed that 7 factors,including gender,vascular invasion,TNM stage,T,lymph node metastasis,distant metastasis and LIPH protein expression level,affected the prognosis of pancreatic cancer patients.There was no correlation with age of onset,presence of nerve invasion,preoperative CA19-9 level,preoperative CA125 level,preoperative CEA level,tumor location,tumor differentiation degree and presence of chronic pancreatitis.Further multivariate analysis showed that positive LIPH expression,TNM stage III-IV,tumor size T₃T₄,and distant metastasis were independent prognostic factors for pancreatic cancer patients.Conclusion:1.LIPH is highly expressed in pancreatic cancer,and the high expression of LIPH can be used as an independent risk factor to judge the overall survival time of pancreatic cancer patients.2.The positive expression of LIPH protein in pancreatic cancer is closely related to the level of CA19-9,the degree of tumor differentiation and whether there is distant metastasis.3.Positive LIPH expression is an independent prognostic indicator in patients with pancreatic cancer.