The Hippo signaling pathway antagonizes the oncogenic transcriptional co-activators yes-associated protein (YAP) and Tafazzin (TAZ) and serves an important role in limiting organ size during developmental processes (5,6). Without the activa- tion of Hippo signaling, non-phosphorylated YAP and TAZ en

TEA Domain Transcription Factors (TEADs) are important in development and serve essential roles in tumorigenesis; however, the role of TEAD2 expression in hepatocellular carcinoma (HCC) has not been widely examined. The present study was conducted to investigate the expression status of TEAD2 in HCC and to evaluate whether the expression of TEAD2 is associated with the prognosis of patients with HCC. mRNA expression data was retrieved for Hippo pathway genes of 50 normal control and 377 HCC samples from The Cancer Genome Atlas data portal. Gene set enrichment, GeneNeighbors, ClassNeighbors and survival analyses were then performed based on the gene expression levels. The mRNA expression of TEAD2 and VGLL4 was significantly higher in HCC compared with the normal control samples, and the mRNA expression of TEAD2 was higher in advanced stages than in early stages. Specifically, survival analysis revealed that higher mRNA expression of TEAD2 was significantly associated with a less favorable overall survival rate (P=0.0067) and there was a trend towards significance between higher mRNA expression of VGLL4 and poor overall survival rate (P=0.051). According to the gene set enrichment analysis, patients with higher mRNA expression of TEAD2 and VGLL4 had strongly enhanced epithelial-mesenchymal transition and angiogenesis, which are associated with tumor progression. In conclusion, increased mRNA expression of TEAD2 is associated with a poor prognosis in patients with HCC. TEAD2 may serve as a prognostic factor for HCC and a novel therapeutic target. Introduction Hepatocellular carcinoma (HCC) was the sixth most common cancer type and fourth most common cause of cancer-associated mortalities worldwide in 2018 (1). Although the various therapeutic modalities for HCC have improved significantly in recent years, patients with HCC exhibit a poor survival rate, with a five‐year survival rate of ~30% (2). Two leading causes of the unfavorable prognosis are delays in the diagnosis of HCC and a lack of appropriate treatment for advanced HCC (3). Although researchers have evaluated the treatment of advanced HCC with immunotherapy or molecular-targeted therapy, the survival rate of patients with HCC has not significantly improved. The occurrence of HCC is thought to be associated with disturbances in the relationships between various genes (4). Therefore, identifying the genes and proteins that regulate HCC development is important for developing novel therapeutic targets (4). The Hippo signaling pathway antagonizes the oncogenic transcriptional co-activators yes-associated protein (YAP) and Tafazzin (TAZ) and serves an important role in limiting organ size during developmental processes (5,6). Without the activation of Hippo signaling, non-phosphorylated YAP and TAZ enter the nucleus and activate the expression of antiapoptotic and proliferative genes with TEA domain transcription factors (TEADs) (5,6). Mammals harbor four TEAD genes (TEAD1‐4). VGLL is a hippo-independent coactivator that regulates gene expression via interaction with TEAD, and there are four VGLL genes (VGLL1‐4). Notably, VGLL4 inhibits tumor growth by binding to TEAD and VGLL1 inhibits YAP/TAZ target genes by competitively binding to TEAD (7-10). Several previous studies revealed that TEADs are involved in human cancer (11-16). However, these studies were primarily focused on TEAD1 and TEAD4, while no clinical studies have examined the association between TEAD2 expression and prognosis in HCC. The purpose of the present study was to investigate the mRNA expression status of TEAD2 in HCC tumors, as well as the prognostic clinical significance of TEAD2 in HCC. Therefore, the role of TEAD2 as a possible prognostic marker and therapeutic target for treating HCC was evaluated. Materials and methods Gene expression profiling. Level 3 mRNA expression aggregated data and clinical data from 50 normal and 377 HCC TEAD2 as a novel prognostic factor for hepatocellular carcinoma JONG SEOk JOO1,2*, SANG YEON CHO1*, WOO SuN ROu1,2, Ju SEOk kIM1,2, SuN HYuNG kANG1,2, EAuM SEOk LEE1,2, HEE SEOk MOON1,2, SEOk HYuN kIM1,2, JAE kYu SuNG1,2, IN SuN kWON3, HYuk SOO EuN1,2 and BYuNG SEOk LEE1,2 1Department of Internal Medicine, Chungnam National university School of Medicine; 2Department of Internal Medicine; 3Clinical Trial Center, Chungnam National university Hospital, Jung-gu, Daejeon 35015, Republic of korea Received August 21, 2019; Accepted February 14, 2020 DOI: 10.3892/or.2020. 7578 Correspondence to: Professor Byung Seok Lee or Professor Hyuk Soo Eun, Department of Internal Medicine, Chungnam National university School of Medicine, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of korea E-mail: gie001@cnuh.co.kr E-mail: liver@kaist.ac. kr *Contributed equally