Analysis Of Expression Profile Of Serum Exosomal MRNAs In Patients With Hepatocellular Carcinoma And The Clinical Significance

BackgroundExsome are small vesicles containing diverse RNAs and proteins,and those secreted from tumor cells carry considerable genetic information of the tumor cells.So,investigations of the specific mRNAs in the exosomes may provide chances for finding new molecular markers and therapeutic targets of tumors.This study was undertaken to investigate the experssion profiles of the exosomal RNAs in hepatocellular carcinoma(HCC)patients and their potential functions by high-throughput screeing and bioinformatics method.PurposeTo study the biological information difference of serum exosome mRNA between hepatocellular carcinoma(HCC)patients and healthy people,trying to provide a theoretical basis and new ideas for finding new molecular markers and therapeutic targets of HCC diagnosis.MethodThe venous blood samples were collected from 3HCC patients and 3 healthy subjects,the serum exosomes were extracted by using exosome isolation kit,and exosomal RNAs were extracted by Magen kit.Then,the serum exosomal mRNAs were purified,reverse-transcribed into cDNAs,amplified by PCR,and identified by sequencing.Finally,the obtained data were compared with the reference data after quality assessment(BAM files)and the differentially expressed exosomal mRNAs were identified and evaluated,and the GO and KEGG Pathway eneichment analysis were used to annotate the function and pathway of the differentially expressed genes.ResultIn HCC patients compared with healthy subjects,there were 397 up-regulated exosomal mRNAs and 192 down-regulated was up-regulated exosomal mRNAs,in which17 genes such as NRGN,PF4 and RGS18 were significantly up-regulated,and 14 genes such as CXCL8,MORE4L2 and SYCP1 were significantly down-regulated.GO enrichment analysis showed that target genes of the up-regulated exosomal mRNAs were related to the protein binding,protein heterodimerization activity,regulation of the immune system process of adjusting and second extracellular vesicles,outside the cell organelles,stress reaction and so on,while the target genes of down-regulated exosomal mRNAs were related to olfatory receptor activity,cytokine activity,CXCR chemokine receptor binding,intermediate filamentous cytoskeleton.KEGG pathway anlysis showed that and 30 pathways were significantly enriched in the up-regulated exosomal mRNAs and 9pathways were significantly enriched in the down-regulated exosomal mRNAs,in which,the platelet activation,RAP 1 signaling pathway,phagocytosis,viral carcinogenesis,regulation of actin cytoskeleton and antigen processing and presentation were the most abundant and significant pathways in the upregulated exosome mRNA,while,the basal transcription factor and cytokine-cytokine receptor interaction were the most abundant and significant pathways in the down-regulated exosomal mRNAs.ConclusionCompared with normal people,HCC patients have large differences in serum exosome mRNA,in which 17 genes such as NRGN,PF4 and RGS18 were significantly up-regulated,and 14 genes such as CXCL8,MORE4L2 and SYCP1 were significantly down-regulated.These differential mRNAs provide a basis for finding new diagnostic markers and therapeutic targets.