Abstract
Senescence marker protein 30 (SMP30) has been identified as a tumor-related molecule of hepatocellular carcinoma (HCC). Its clinical significance and underlying mechanisms in HCC tissues, however, remain largely unexplored. We have demonstrated a preferentially expressed SMP30 in normal liver using a tissue microarray. By employing real-time quantitative PCR, two tissue microarrays and Oncomine database analysis, we have also shown that the SMP30 in HCC tissues has significantly reduced when compared with that in paired adjacent non-tumor tissues (P = 0.0037). The reduced expression of SMP30 is very noticeably related to larger tumor size (P = 0.012), enhanced TNM (P = 0.009) and worse survival (P < 0.0001) in HCC patients. The analyses using Cox regression have indicated that the decreased SMP30 expression is an independent risk to the reduced overall survival rate of HCC patients (P = 0.001), and the down-regulation of SMP30 in HCC might be mediated by DNA methylation. Moreover, genes co-expressed with SMP30 may affect the prognosis through apoptotic process, biological adhesion and blood coagulation by PANTHER analyses. Our studies have indicated that the SMP30 may serve as a candidate of HCC clinical prognostic marker and a potential therapeutic target.
Highlights
It is well known that majority (70–90%) of primary hepatic carcinoma diagnosed worldwide is hepatocellular carcinoma (HCC)[1] and that the highest liver cancer incidence is found in East and South-East Asia, followed by Northern and Western Africa[2]
The investigations of Senescence marker protein 30 (SMP30) expression status associated with the clinicopathological features and prognostic significance in HCC tissues, have not been reported
We have discovered that lower SMP30 staining significantly associates with larger tumor size and enhanced TNM in HCC patients
Summary
It is well known that majority (70–90%) of primary hepatic carcinoma diagnosed worldwide is hepatocellular carcinoma (HCC)[1] and that the highest liver cancer incidence is found in East and South-East Asia, followed by Northern and Western Africa[2]. Advances in medicines have raced ahead in the treatment of HCC, its long-term survival rate is limited by the high rate of recurrence and metastasis after surgery[3]. It is unclear, how the molecular mechanism contributes to recurrence and metastasis of HCC. The correlations between SMP30 expression and prognostic significance in HCC, have not been reported. The purpose of this research work is to investigate the SMP30 expression status in human normal tissues, in HCC tissues and in their adjacent non-tumor tissues. The SMP30 expression and its correlations with clinical characteristics including overall survival (OS) rate have been assessed. We have discussed the main mechanism that account for SMP30 losses in HCC patients and performed a biologic process analysis of genes co-expressed with SMP30
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