ABSTRACT
Objective To investigate the expression of centromere protein F(CENPF)in pancreatic ductal adenocarcinoma(PDAC)and its relationship with the clinicopathological features and prognosis of patients.Methods Based on Gene Expression Omnibus(GEO)from National Center for Biotechnology Information(NCBI),using GEO2R,Venn diagram,Cytoscape,MCODE and GEPIA software to screen out the suspected differential gene CENPF in PDAC;based on the Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx),using NCBI,GEPIA,Ualcan,Oncomine,TIMER software and Kaplan-Meier on-line survival analysis tool to analyze its possible molecular mechanism from the level of messenger RNA(mRNA).In all,surgical specimens of 121 PDAC cases diagnosed at the pathology department of the First Affiliated Hospital of Fujian Medical Univer-sity were analyzed from the histoprotein level to analyze the relationship between CENPF and clinicopathological features and prognosis of PDAC.Results CENPF gene was abnormally expressed in various human cancers,and there was a difference in expression between pancreatic ductal adenocarcinoma and normal pancreatic tissue(P＜0.05),and it was related to the grading(P＜0.05)and prognosis(P=0.038)of pancreatic ductal adenocarcinoma.Immunohistochemistry showed that the expression of CENPF was correlated with nerve invasion(P=0.036),TNM stage(P=0.041),lymph node metastasis(P=0.023),degree of differentiation(P=0.020)and overall survival of pancreatic ductal adenocarcinoma(Log-rank=18.608,P=0.000016),and CENPF expression(HR=2.654,95％CI=1.373-5.131,P=0.004)was an independent risk factor for the prognosis of PDAC patients.CENPF combined with other key module genes in PDAC was mainly enriched in exosomes,extracellular mechanisms,and was related to serine endopeptidase activity and metalloendopeptidase activity.The action pathway of CENPF single gene in pancreatic ductal adenocarcinoma was mainly related to cell cycle,P53 pathway,ubiquitin-mediated proteolysis,and played a joint role with P53 and MDM2 in PDAC.Immune infiltration studies showed that CENPF expression was negatively correlated with CD4+T lymphocyte infiltration and positively correlated with dendritic cell infiltration(both P＜0.05).Conclusion CEN-PF may be involved in the progression of PDAC,and high expression of CENPF indicates a poorer prognosis.Our research is expected to provide more scientific evidence for the prevention and treatment of PDAC.
ABSTRACT
Objective To investigate the relationship between the expression of CENPF in NSCLC adenocarcinoma (LUAD) and the clinical prognosis of patients and its effect on the metastasis of lung adenocarcinoma cells. Methods The expression of CENPF in LUAD and its relationship with patient prognosis were analyzed by online bioinformatics. The expression of CENPF was verified by LUAD tissue microarray immunohistochemical staining. Kaplan-Meier analysis was performed to analyze the relationship between the expression of CENPF and the prognosis of patients with lung adenocarcinoma. Cox survival hazard ratio was used to analyze the factors affecting the survival of patients. Chi-square analysis was adopted to examine the relationship between CENPF expression and clinicopathological stage and grade of patients. The expression of CENPF in NCI-H2126 cells were knocked out by lentivirus, and then the proliferation, invasion, and migration abilities of the cells were detected. Changes in mRNA expression profiles after CENPF knockout were detected by RNA-seq. Bioinformatics analysis of downstream signaling pathways and the target genes of CENPF was also performed. Western blot was used to verify the target gene. Results CENPF was significantly upregulated in LUAD tumor tissue (P < 0.05) and significantly correlated with pathological stage (P=0.013). The higher expression of CENPF, the worse the prognosis of patients (P=0.01, P=0.027). After the expression was CENPF of knocked out, the cell proliferation, migration, and invasion abilities significantly reduced (P < 0.01). The expression of chemokine pathway genes in cells was enriched significantly (P < 0.001). ACKR3/CXCR7 and CDH2/N-cadherin were significantly downregulated, whereas CDH1/E-cadherin was significantly upregulated. After CENPF was knocked out, ACKR3/CXCR7 and N-cadherin were significantly downregulated, whereas E-cadherin significantly increased. Conclusion The expression of CENPF is negatively correlated with the clinical prognosis of patients with LUAD, and it promotes the occurrence of EMT by regulating the expression levels of N-cadherin and E-cadherin related to EMT through ACKR3/CXCR7.