Establishment And Validation Of A Signature For Hepatocellular Carcinoma Based On Solute Carrier Genes

Background: Hepatocellular Carcinoma（HCC）is one of the most common types of primary liver cancer,and its treatment remains difficult.Because the early symptoms of hepatocellular carcinoma are not obvious,many patients with hepatocellular carcinoma are at advanced stages when diagnosed.Although current targeted therapies and immunotherapies have achieved initial efficacy in patients with liver cancer,some patients still experience low response rates or drug resistance,which leads to tumor progression or even patient death.Therefore,new biomarkers are urgently needed to predict patients’ prognosis and guide treatment.Transporter proteins are membrane-bound proteins that mediate the transport of substrates across biological membranes.Membrane transport proteins are widely expressed in epithelial cells of major organs throughout the body,such as liver,intestine,kidney,and epithelial cells of organs with barrier function.Among the transporter proteins,Solute carrier（SLC）transporter proteins are mainly involved in the entry of small molecules into cells.In recent years,solute carrier transport proteins have been found to be closely related to the development and progression of many types of tumors.Therefore,investigating the role of solute carrier transporter proteins in the progression of hepatocellular carcinoma may provide new ideas for studying the development and progression of hepatocellular carcinoma as well as its treatment.Objective: To construct a signature of solute carrier transporter protein hepatocellular carcinoma and further explore the related immune microenvironment and molecular regulatory network to provide new directions for prognostic monitoring and individualized treatment of hepatocellular carcinoma.Methods: The Cancer Genome Atlas（TCGA）database was used to obtain transcriptomic and clinically relevant data from patients with liver cancer,and univariate COX analysis was used to screen for solute carrier proteins associated with liver cancer prognosis into the Least absolute shrinkage and selection operator（LASSO）regression prediction.Statistical,functional and clinical prediction analyses were performed to construct a signature for hepatocellular carcinoma based on nine genes associated with SLC transport proteins.The predictive value of the signature was validated in the International Cancer Genome Consortium（ICGC）liver cancer external dataset.Gene Set Enrichment Analysis（GSEA）,immune infiltration,and immune checkpoint correlation analyses were performed on the high-and low-risk groups of the signature.Clinical specimens of fresh liver cancer tissues were obtained to identify tumor and normal tissues by HE staining method.Then we detected the signature Hub gene expression by q RT-PCR method.Results: Through comprehensive analysis,a prognostic marker for liver cancer consisting of nine SLC genes was constructed in this study.By calculating the risk score,patients with hepatocellular carcinoma could be divided into two groups: high-risk and low-risk,and the high-risk group had a significantly worse prognosis.By enrichment analysis we found that the high-risk group was associated with gene ontology（GO）functions such as B-cell activation,B-cell-mediated related immunity.We also found that the expression of most of the immune checkpoints differed between the high and low risk groups.In addition,this study also identified a Hub gene: solute carrier 7family 11（SLC7A11）,which may be an important potential prognostic marker for liver cancer.In conclusion,this study may provide a reference for the prognostic assessment and treatment of hepatocellular carcinoma.Conclusion:（1）This study constructed a signature for hepatocellular liver cancer based on nine SLC genes.By calculating risk scores,patients with hepatocellular carcinoma were divided into high-and low-risk groups.（2）By further analysis of the high-and low-risk groups,the study found differences in immune cell infiltration and expression of immune checkpoint genes in different risk groups.（3）In addition,the study identified the Hub gene of the signature:SLC7A11,which may be an important oncological marker for liver cancer prognosis.After identification of hepatocellular carcinoma tissues by HE staining,q RT-PCR experiments verified its differential expression in tumor and pericarcinomatous tissue.