High expression of GNA13 is associated with poor prognosis in hepatocellular carcinoma

Abstract

Guanine nucleotide binding protein alpha 13 (GNA13) has been found to play critical roles in the development of several human cancers. However, little is known about GNA13 expression and its clinical significance in hepatocellular carcinoma (HCC). In our study, GNA13 was reported to be significantly up-regulated in HCC tissues, and this was correlated with several clinicopathological parameters, including tumor multiplicity (P = 0.004), TNM stage (P = 0.002), and BCLC stage (P = 0.010). Further Cox regression analysis suggested that GNA13 expression was an independent prognostic factor for overall survival (P = 0.014) and disease-free survival (P = 0.005). Moreover, we found that overexpression of GNA13 couldn't promote cell proliferation in vitro, but could significantly increase the invasion ability of HCC cells. Together, our study demonstrates GNA13 may be served as a prognostic biomarker for HCC patients after curative hepatectomy, in which high expression of GNA13 suggests poor prognosis of HCC patients.

Figure 1. The expression of GNA13 in HCC by Western blotting and qPCR.

(A) Among 12 HCC cases, increased expression of GNA13 was detected via western blotting in 10 pairs of HCC tissues compared with the matched non-cancerous liver tissues. The expression levels were normalised to those of GAPDH. (B) The mRNA expression of GNA13 was significantly upregulated in 10/12 pairs of HCC tissues based on qPCR. The expression levels were normalised to those of GAPDH. N, adjacent normal liver tissue; T, HCC tissue.

Figure 2. Representative images of GNA13 expression in adjacent non-cancerous liver tissues and HCC tissues via IHC.

GNA13 was absent or only weakly detected in adjacent normal liver cells (A), whereas its upregulation was mainly detected in HCC tissues (B) (original magnification, x100 and x400)(Left). The box plot showed the mean staining score of GNA13 in HCC tissues (T) and the adjacent non-cancerous liver tissues (N) (P < 0.001)(Right).

Figure 3. The protein expression of GNA13 in HCC by immunohistochemistry.

The representative images show different staining intensities of GNA13: (a) negative staining, (b) weak staining, (c) moderate staining, and (d) strong staining (original magnification, x100 and x400).

Figure 4. Survival analysis of GNA13 expression by Kaplan-Meier method.

Overall survival rate and disease-free survival rate in total (A,B) HCC patients with low/high GNA13 expression. Overall survival rate and disease-free survival rate in tumor size > 5 cm (C,D), TNM stage III/IV (E,F), and pathological grade III/IV (G,H) HCC patients with low/high GNA13 expression.

Figure 5. Effect of GNA13 overexpression on cell proliferation and invasion in vitro.

(a) Overexpression of GNA13 could not promote the proliferation of HepG2 and SMMC-7721 cells in vitro as determined by MTT assay. (b) In the invasion assay, the cell invasion ability was significantly increased after overexpression of GNA13 in HepG2 and SMMC-7721 cells when compared with Vector control. Bars represent the mean ± SD of three independent experiments. *P < 0.05.