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Oncol Rep. 2014 Jun;31(6):2569-78. doi: 10.3892/or.2014.3125. Epub 2014 Apr 2.

Expression and significance of the novel tumor-suppressor gene SMG-1 in hepatocellular carcinoma.

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  • 1Department of Oncology, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
  • 2Department of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.


Recent studies have demonstrated that SMG-1, a newly characterized member of the family of phosphatidylinositol 3-kinase-related protein kinases (PIKKs), is involved in tumorigenesis as a new tumor suppressor. However, its expression and significance in hepatocellular carcinoma (HCC) remain obscure. The present study investigated SMG-1 expression in HCC tissue specimens, aimed at defining the association with clinicopathological significance. Both immunohistochemistry and qRT-PCR were employed to analyze SMG-1 expression in 157 HCC and corresponding distant normal tissue specimens. The results revealed that expression of SMG-1 was significantly lower in the HCC tissue specimens than that in the distant normal tissues. Moreover, a lower expression level of SMG-1 was significantly correlated with serum α-fetoprotein level (P=0.001), poorly differentiated tumors (P=0.009) and more advanced TNM stage (P<0.001). Further study showed that SMG-1 expression was exactly associated with tumor differentiation and clinical stage in HCC. Kaplan-Meier analysis indicated that low SMG-1 expression was related to poor overall survival, and the prognostic impact of SMG-1 was further confirmed by stratified survival analysis. Importantly, multivariate analysis revealed that low SMG-1 expression was an independent prognostic marker for an unfavorable overall survival. We conclude that SMG-1 is downregulated in HCC and may represent a promising biomarker for predicting the prognosis of HCC, including the prognosis of early-stage patients.

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