Bioinformatic study of GPC۳ gene in liver cancer

Primary liver cancer is the fourth leading cause of cancer related death around the world .We can divide this cancer into two groups as hepatocellular carcinoma (۷۵% of all liver cancer) and intrahepatic cholangiocarcinoma (۱۵%). liver cancer usually happens in liver disease or cirrhosis patients. The country of provenance and etiology are affective in the risk factors for developing Hepatocellular Carcinoma. Hepatocellular carcinoma (HCC) happens when hepatocytes develop mutation in their DNA and more than ۱۲۰۰۰ deaths occur annually in The United States because of HCC. Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) , cirrhosis which is the progressive and irreversible condition causes scar livers tissue , diabetes , excessive alcohol consumption , and accumulation fat in body increase the liver cancer. In this study , bioinformatics analysis was performed to find a novel mRNA , miRNA and lncRNA that are effect in liver cancer. GEO analysis help us to select a significant gene for subsequent bioinformatics analysis. Methods: First we obtained GSE۱۴۷۸۸۸ from Gene Expression Omnibus(Geo). Then we analyzed it by Geo۲R to obtain differentially expressed genes . By this analyzed data we found a gene that is suitable (Adj P. value <۰>۱) and we selected GPC۳ gene for future studies. And then pathways are found by Kegg Database , gene product protein by Uniprot , Snp by dbsnp to find snp in coding region sequence and Mirnasnp to find snp in ۳UTR , LncRNA by LNCRRESEARCH & LNCBASE v۳ and miRNA by MIRWALK . We used MIRWALK database to find the miRNA that has the interaction with our selected mRNA in coding region sequence . We used LNCBASE v.۳ and searched this miRNA to find interactions with lncRNAs. Also we used STRING database to find protein _protein interactions that effective in liver cancer . Results: According to the GEO analysis , GPC۳ is determined as an up regulated gene (with ۶.۱۰۸ Log FC) in tumor samples compared to normal samples , and this result was confirmed by GEPIA۲ and ENCORI. Based on Enrichr database GPC۳ inference in proteogelicans in cancer pathway. Protein - protein analysis for our gene (GPC۳) showed that these related proteins have role in proteoglycans in cancer that is a pathway related our selected gene. Based on miRNA – mRNA interactions analysis, a miRNA named has -miR-۶۷۵۵-۵p obtained as a novel significant miRNA to GPC۳ mRNA in liver cancer . In addition KCNQ۱۰T۱ was found as a novel lncRNA that related to GPC۳ mRNA that we obtained this by LNCRRESEARCH . Also, we found a miRNA named has-let -۷a-۳p that have interaction with KCNQ۱۰T۱(our lncRNA). Conclusions : According to the all mentioned analysis , the GPC۳ gene is an over –expressed gene in liver cancer which could be associated with mortality in this disease. This can regulate proteoglycans in cancer pathway which play significant roles in the development of liver cancer.

کلیدواژه ها:

Liver cancer ، Bioinformatics ، GPC۳ gene ، snp ، pathway