Background and Aims: Glia maturation factor β (GMFB) is a 17 kDa and highly conserved brain-specific protein. Recent investigations demonstrated that GMFB expression is up-regulated in variety of cancers and closely associated with the unfavorable outcomes of the patients. However, the knowledge about the expression and function of GMFB in hepatocellular carcinoma (HCC) is still insufficient. This study was designed to investigate the clinical significance of GMFB in HCC by examining the expression of GMFB in HCC tissue and analyzing its relations with the clinicopathologic features and prognosis as well as Ki-67 expression of the patients.
Methods: The mRNA and protein expressions of GMFB in 36 paired fresh-froze HCC and adjacent tissue were determined by qRT-PCR and Western blot respectively. The protein expressions of GMFB and Ki-67 in 91 paired paraffin specimens of HCC and adjacent tissue were determined by immunohistochemical staining. The relations of GMFB expression with the clinicopathologic factors and postoperative survival time of the patients as well as Ki-67 expression were analyzed by statistical methods.
Results: The results of qRT-PCR and Western blot showed that the relative expression levels of both GMFB mRNA and protein in HCC tissue were significantly higher than those in tumor adjacent tissue (both P<0.001). The results of immunohistochemical staining showed that the positive expression rates of both GMFB and Ki-67 in HCC tissue were significantly higher than those in tumor adjacent tissue (both P<0.001); GMFB expression was significantly related to the microvascular invasion (P=0.045), Edmondson grade (P=0.032) and BCLC stage (P=0.012); there was a positive correlation between GMFB expression and Ki-67 expression in HCC tissue (rs=0.265, P=0.011). Kaplan-Meier survival analysis showed that disease-free survival (DFS) and overall survival (OS) in patients with positive GMFB were significantly shorter than those in patients with negative GMFB expression (DFS: 4.52 months vs. 10.48 months, P=0.001; OS: 27.67 months vs. 39.75 months, P=0.007). Cox multivariate regression analysis showed that the upregulations of GMFB and Ki-67 were independent risk factors for both DFS (HR=0.441, 95% CI=0.242–0.801, P=0.007; HR=1.818, 95% CI=1.012–3.269, P=0.046) and OS (HR=0.504, 95% CI=0.287–0.886, P=0.017; HR=1.787, 95% CI=1.083–2.935, P=0.023) of HCC patients.
Conclusion: GMFB presents a high expression in HCC, and is closely associated with tumor progression and poor prognosis of the patients. GMFB expression is positively correlated with Ki-67 expression, suggesting that GMFB exerts its actions by regulating the proliferative ability of the cancer cells.