Abstract
SCAMP3, an isoform of the secretory carrier membrane proteins (SCAMPs) family, is a membrane-trafficking protein involved in endosome transport. Previous microarray data showed that SCAMP3 mRNA is highly expressed in hepatocellular carcinoma (HCC). In this study, the expression and clinical significance of SCAMP3 in 100 pairs of HCC and adjacent normal tissue were investigated. siRNA transfection was performed to silence SCAMP3 expression in HCC cells. The MTS assay and flow cytometry were used to detect the proliferation, cell cycle progression of HCC cells. Compared with adjacent normal tissues, SCAMP3 expression was dramatically increased in HCC tissues demonstrated by Western blotting (P < 0.05). In immunohistochemistry, compared with the adjacent normal tissues, SCAMP3 was detected in 96% of the HCC samples with a significant increase in intensity and number of stained cells (P < 0.05). Also, high SCAMP3 expression was found in 86% of the HCC samples (P < 0.05). The increased SCAMP3 expression was significantly correlated with vascular invasion (P = 0.004) and tumor stage (P = 0.001). Univariate and multivariate survival analyses showed that the expression of SCAMP3 was an independent prognostic factor of overall survival of HCC patients. Knockdown of SCAMP3 expression led to suppression of cell proliferation and blockage of cell cycle of HCC cells. In conclusion, our present study suggested that SCAMP3 may serve as a promising prognostic biomarker and molecular target of HCC and further investigation is warranted.
Highlights
The liver cancer is the most common primary malignancy of the liver and it is the sixth most common cancer worldwide [1]
The result showed that the expression of SCAMP3 was dramatically increased in hepatocellular carcinoma (HCC) tissues compared with the adjacent normal tissues (Figure 1A)
The ratio of SCAMP3 expression to GAPDH was displayed in a bar chart showing a significant higher expression of SCAMP3 in HCC tissues than in the adjacent normal tissues (Figure 1B, *P < 0.01)
Summary
The liver cancer is the most common primary malignancy of the liver and it is the sixth most common cancer worldwide [1]. Hepatocarcinogenesis has a complicated course, which presents with a series of www.impactjournals.com/oncotarget genetic and epigenetic changes that occur during initiation, promotion, and progression of the disease These changes include gene mutations, modifications of oncogenes and tumor-suppressor genes, copy number variations and gene rearrangements, epigenetic modifications and alterations in numerous signaling pathways [6,7,8]. The function of SCAMPs is not yet known, several previous studies suggested that SCAMPs may play a crucial role in exocytosis and vesicle budding in mammalian cells [12,13,14]. SCAMP3 was one of those eight genes located in 1q22 and was significantly up regulated in both mathematical models [19] Those previous studies emphasized the importance of SCAMP3 and supported a hypothesis that SCAMP3 may play a role in the pathogenesis of HCC. The effect of SCAMP3 knockdown in cell cycle and cell proliferation of HCC cells were investigated
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