Evaluation of TGFß, XPO4, elF5A2 and ANGPTL4 as biomarkers in HCC.

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and the fourth leading cause of cancer mortality worldwide. It is often diagnosed at an advanced stage, and hence typically has a poor prognosis. A number of distinct molecules have been recently identified as playing a role in the control of cancer progression. However, patients with HCC have a highly variable clinical course, indicating that HCC comprises several biologically distinctive subgroups reflecting a molecular heterogeneity of the tumors. To evaluate potential biomarkers in HCC, we employed multiple methods in this study, including qPCR, immunostaining methods and tissue microarrays (TMAs), as well as histological and pathological analysis, to assess TGFß, XPO4, elF5A2 and ANGPTL4 in cancerous and paracancerous liver tissues from 280 patients suffering from liver cancer. Our results found that all four indicators were located in the cytoplasm and distributed in cancerous and paracancerous liver tissues. Generally, there were higher levels of these indicators in paracancerous, compared with cancerous, liver tissues. These four indicators were correlated and modulated among each other. In connection with patient clinical and revisit information, statistical analysis determined that TGFß1 in paracancerous liver tissue was positively correlated with tumor size. Higher production of TGFß1 in paracancerous liver tissue was always associated with bigger liver tumors. XPO4 in cancerous liver tissue and TGFß1 in paracancerous liver tissue were positively correlated with tumor differentiation. TGFß1, ANGPTL4 and elF5A2 were also positively correlated with the T classification of tumors. Additionally, higher levels of XPO4 in cancerous liver tissue suggested that the patient would have a better prognosis and survival rate. However, higher production of XPO4 in paracancerous liver tissue suggested a worse prognosis. All the results above provide new insights into better understanding biological indicators, such as XPO4, TGFß1, ANGPTL4 and elF5A2, in the prediction and evaluation of liver cancer, as well as signaling pathways in the control of liver cancer. XPO4 and TGFß1 may serve as useful markers to evaluate the size and prognosis of liver cancer.