The prognostic role and reduced expression of FOXJ2 in human hepatocellular carcinoma

Abstract

The current study aimed to investigate the potential role of the FOXJ2 (forkhead box J2) protein in the pathology of hepatocellular carcinoma (HCC). Western blotting was performed to determine the expression levels of FOXJ2 in HCC tissues and HCC cells. Specimens from 110 patients with HCC undergoing hepatic resection were evaluated for FOXJ2 expression using an immunohistochemical assay. The correlation between FOXJ2 expression and clinicopathological factors of the patients was determined by statistical analysis to determine the prognostic merit of FOXJ2 expression in HCC. The detailed involvement of FOXJ2 in the regulation of HCC proliferation was further investigated using FOXJ2-targeting small interfering RNA (siRNA). FOXJ2 protein was identified to be significantly downregulated in HCC tissues compared with adjacent normal liver tissues. Immunohistochemical analysis demonstrated that the expression of FOXJ2 was negatively correlated with Ki-67 levels in HCC specimens (r=−0.679, P<0.001). Furthermore, statistical analysis indicated FOXJ2 expression was significantly associated with histological differentiation (P=0.005), the size of largest tumor (P=0.002) and metastasis (P=0.036). Using Kaplan-Meier analysis, it was demonstrated that high FOXJ2 expression levels predicted significantly improved patient survival rates compared with low FOXJ2 expression levels (P<0.001). In addition, it was observed that interference of FOXJ2 expression using siRNA oligos led to the promotion of proliferation of HepG2 cells. FOXJ2 was markedly downregulated in HCC tissues. The expression of FOXJ2 was correlated with tumor size, histological differentiation and metastasis. Low expression levels of FOXJ2 predicted poor prognosis for patients with HCC, suggesting that FOXJ2 may be a candidate prognostic marker of HCC. Depletion of FOXJ2 caused the promotion of HCC cell proliferation, implicating that FOXJ2 may serve an inhibitory role in the regulation of HCC cell proliferation.

Phosphoglucomutase 1 inhibits hepatocellular carcinoma progression by regulating glucose trafficking

“…Among the predicted transcription factors, FOXJ2 was the first transcriptional factor that might regulate PGM1 expression and was also reported to suppress tumor growth. FOXJ2 is a member of the forkhead transcription factor family [ 16 ] and was down-regulated in HCC and extrahepatic cholangiocarcinoma [ 17 , 18 ]. We therefore tested whether FOXJ2 regulates PGM1 expression.…”

“…As described in Fig 1E and 1F , decreased PGM1 expression correlated with poor prognosis of HCC patients. FOXJ2 expression has also been suggested to correlate with poor prognosis of HCC patients [ 18 ]. To determine prognostic potential of integrated analyses of PGM1 and FOXJ2 expression, we divided 272 HCC patients into 2 groups.…”

“…FOXJ2 is a member of the forkhead transcription factor family [ 16 ] and was down-regulated in HCC and extrahepatic cholangiocarcinoma [ 17 , 18 ]. FOXJ2 has been suggested to function as a tumor suppressor gene in breast cancer cells, glioma cells, cholangiocarcinoma cells, HCC cells, and non–small-cell lung cancer, and low expression levels of FOXJ2 indicates poor prognosis of cancer patients [ 17 , 19 , 27 , 28 ].…”

Low FOXJ2 expression is associated with unfavorable postoperative prognosis of patients with epithelial ovarian cancer

“…[ 14 ] In addition, FOXJ2 could also inhibit the proliferation of human hepatocellular carcinoma cells, and reduced expression of FOXJ2 was significantly associated with the poor prognosis of patients with human hepatocellular carcinoma. [ 20 ] The present study revealed that low FOXJ2 expression was associated with advanced FIGO stage by assessing 151 epithelial ovarian cancer cases. Besides, FOXJ2 expression was significantly different regarding treatment approaches.…”

“…[ 13 – 17 ] FOXJ2 was shown to positively regulate cell cycle progression and induce tumorigenesis. [ 18 , 19 ] However, FOXJ2 was described as a tumor suppressor in liver cancer, [ 20 ] indicating that its exact function in cancer deserves further investigation.…”