Abstract
Recent studies have demonstrated an oncogenic role of the transcription factor (TF) CP2c in hepatocellular carcinoma (HCC) based on a strong correlation between CP2c expression, tumor grade, and aggressiveness. We recently found that CP2c directly interacts with another TF, YY1, which is also overexpressed in multiple cancers, including HCC. To evaluate if these proteins are co-regulated in carcinogenesis, we analyzed the expression of CP2c and YY1 in HCC (n = 136) tissues and examined the correlation between their expression and clinicopathological characteristics of HCC. Receiver operating characteristic analysis exhibited the validity of CP2c and nuclear YY1 expression as a diagnostic factor in HCC tissues. High expression of CP2c was significantly correlated with patient age, and higher histological grade, American Joint Committee on Cancer (AJCC) stage, and small and large vessel invasion in HCC tissues, whereas high expression of nuclear YY1 was significantly associated with higher AJCC stage and small vessel invasion. In univariate and multivariate analyses, high expression of CP2c was significantly correlated with disease free survival (DFS), indicating that CP2c expression is an independent prognostic factor for DFS in HCC patients. Patients with high expression of both CP2c and nuclear YY1 usually had a shorter median survival time and worse DFS prognosis than other patients, suggesting that combined detection of CP2c and nuclear YY1 is a useful prognostic marker in HCC patients.
Highlights
Transcription factor (TF) CP2c was first identified as a transcriptional activator of the α-globin gene in erythroid cells [1,2]
CP2c was expressed at significantly higher levels in hepatocellular carcinoma (HCC) tissues than normal liver or adjacent noncancerous (ADJ) liver tissues, whereas YY1 was expressed at lower levels in HCC compared with normal or noncancerous liver tissues (Figure 1A)
These data indicate that CP2 family and YY1 proteins, which are components of a joint transcription factor (TF) network, are differentially expressed in noncancerous liver and HCC tissues, suggesting that they may play a coregulatory role in HCC development and/or progression
Summary
Transcription factor (TF) CP2c ( known as TFCP2, α-CP2, LSF, and LBP-1c) was first identified as a transcriptional activator of the α-globin gene in erythroid cells [1,2]. CP2c, a member of the CP2 family of proteins, participates in diverse processes including hematopoiesis, immune response, cell cycle, and neural development by regulating the expression of specific target genes [5]. Interactions between CP2c and other isoforms of the CP2 family as well as various partner proteins, allow for the regulation of specific target genes in different cellular environments [6,7,8,9,10,11]. It was found to confer 5-FU resistance to HCC cell lines by activating the expression of thymidylate synthase (TS) gene [16,17,18]. CP2c was shown to activate osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) expression and regulate invasion, metastasis, and angiogenesis of www.impactjournals.com/oncotarget
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