Study On Tumor Markers Of Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma(HCC)as a malignant tumor placed in the third highest mortality in our country.In the HCC prone population,early diagnosis and detection of HCC could facilitate early surgical treatment and improve the survival rate of patients.Current diagnostic methods for HCC include liver cancer imaging and serum markers detection.However,the imaging methods,which showed lower sensitivity in early tumor detection,usually be utilized in the late or advanced stages of liver cancer.In present,main liver cancer specific markers were alpha fetal protein(AFP)and ?-glutamyl-transferase(GGT).Although AFP improved the diagnostic rate in clinic as a specific marker of liver cancer,it has also been expressed in gastric cancer,liver cirrhosis and chronic hepatitis,so using single AFP index to monitor the liver cancer prone to false positive,misdiagnosis,or missed diagnosis and so on.GGT was also expressed higher in most normal liver and gallbladder,and it cannot distinguish the primary liver cancer from the secondary liver cancer.Therefore,to develope more specific markers are very important for the early diagnosis of hepatocellular carcinoma.ObjectiveThis study aims to identify new biomarkers for HCC,thus providing theoretical basis for early diagnosis,risk prediction and treatments of liver cancer.Methods1.The HCC related genes were analyzed by GEO database,and then through the websites of David,Passway Studio,GENE ONTOLOGY,NCBI,KEGG,GENMAPP and BIOCARTA,the identified HCC related genes were classified according to their gene types and signal transduction pathways.Finally,key HCC related genes were determined and studied.2.The morphological characteristics of the hepatocellular carcinoma and adjacent tissue samples for 17 patients were collected and verified accurately by HE staining method.3.The expression of VCAM-1,MMP2,MMP9,P53,KIF1 B,ARID1A,ERCC3 were detected and analyzed by Quantitative Real-time PCR,Western blotting and immunohistochemistry..Results1.In this study,we retrieved the whole genome sequencing results of liver cancer tissues and adjacent tissues in the GEO database.More than 28000 genes were discovered in the database,1408 genes' expression changes were significant.These genes were analyzed for physiological activities and molecular function annotation in Gene Ontology,indicated that these genes were mainly involved in the negative regulation of cell proliferation,migration,apoptosis and other important physiological activities.Then the genes were analyzed by means of the KEGG classical pathway,and the data showed that these genes played key roles in MAPK,Jak-STAT,and all kinds of cancer signaling pathways.Combined with GO notes and Pathway KEGG analysis,the high degree of cross-linking genes of VCAM-1,MMP2,MMP9,P53,KIF1 B,ARID1A and ERCC3 were picked out for further study.2.The liver cancer tissues and its adjacent tissues of 17 patients were identified accurately by HE staining.qRT-PCR results showed that there was no difference in the expression of KIF1 B and ERCC3 in liver cancer and adjacent tissues.However,the expression of P53,MMP2,VCAM-1,MMP9 and ARID1 A in HCC tissues was higher than that in the adjacent tissues with significant difference.In addition,we verified the results of qRT-PCR through the Western blot.The results of immunohistochemical study demonstrated that VCAM-1,MMP2,MMP9,ARID1 A,P53 were highly expressed in hepatocellular carcinoma.ConclusionsVCAM-1,MMP2,MMP9,ARID1 A,P53 can be used as potential means of early diagnosis of HCC,providing help for the diagnosis of HCC.