Investigation of proprotein convertase subtilisin/kexin type 9 expression in colorectal cancer and its impact on cell migration
Objective To explore the expression levels of proprotein convertase subtilisin/kexin type 9(PCSK9)in colorectal cancer(CRC)and its effects on the proliferation and migration of CRC cells.Methods This study analyzed the differential expression of PCSK9 in normal and CRC tissues by analyzing The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases;the relationship between PCSK9 expression and CRC prognosis was assessed using the GenomicScape database;PCSK9 protein expression levels were evaluated using an immunohistochemical method in a tissue microarray chip containing 93 human colon cancer cases and 85 adjacent normal tissues.Gene set enrichment analysis(GSEA),Kyoto encyclopedia of genes and genomes(KEGG)and gene ontology(GO)enrichment analyses were conducted using the TCGA database;the role of PCSK9 in CRC was explored through human recombinant protein stimulation experiments.Results TCGA database analysis results showed that compared with the normal tissues,the mRNA expression levels of PCSK9 in various tumor types such as colon adenocarcinoma,rectum adenocarcinoma were up-regulated,the differences were statistically significant(all P<0.05).Analysis results of 4 datasets showed that compared with normal tissues,the mRNA expression levels of PCSK9 in tumor tissues of CRC patients from America(t=12.07),Germany(t=12.72),China(t=12.13)and Norway(t=13.38)were up-regulated,the differences were statistically significant(all P<0.05).The protein level of PCSK9 was significantly upregulated in tumor tissues of CRC than that in normal tissues(P<0.05).The low expression group had higher overall survival than the PCSK9 high expression group,the difference was statistically significant(HR=2.6,P<0.05).GO and KEGG enrichment analysis showed that PCSK9-related genes were enriched in various biological processes such as DNA replication,mismatch repair and cell cycle.Transwell migration assay indicated that the migration ability of CRC cells HCT116 treated with 20 and 100 ng/mL recombinant human PCSK9 were stronger than that in control group(t=7.73,12.10),the migration ability of CRC cells DLD1 treated with 20 and 100 ng/mL recombinant human PCSK9 were stronger than that in control group(t=3.79,6.51).The differences were statistically significant(all P<0.05).Wound-Healing assay indicated that the wound-healing ability of HCT116 cells treated with 100 ng/mL recombinant human PCSK9 were stronger than that in control group(t=3.29),the migration ability of DLD1 cells treated with 20 and 100 ng/mL recombinant human PCSK9 were stronger than that in control group(t=4.21,10.83).The differences were statistically significant(all P<0.05).Conclusions PCSK9 was highly expressed in CRC tissues and was associated with poor prognosis.Furthermore,stimulation by PCSK9 might promote the migration of CRC cells.
Proprotein convertase subtilisin/kexin type 9Colorectal cancerCell migration
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