Abstract
The high incidence of recurrence and the poor prognosis of hepatocellular carcinoma (HCC) necessitate the discovery of new predictive markers of HCC invasion and prognosis. In this study, we evaluated the expression pattern of two members of a novel oncogene family, Musashi1 (MSI1) and Musashi2 (MSI2) in 40 normal hepatic tissue specimens, 149 HCC specimens and their adjacent non-tumourous tissues. We observed that MSI1 and MSI2 were significantly up-regulated in HCC tissues. High expression levels of MSI1 and MSI2 were detectable in 37.6% (56/149) and 49.0% (73/149) of the HCC specimens, respectively, but were rarely detected in adjacent non-tumourous tissues and were never detected in normal hepatic tissue specimens. Nevertheless, only high expression of MSI2 correlated with poor prognosis. In addition, MSI2 up-regulation correlated with clinicopathological parameters representative of highly invasive HCC. Further study indicated that MSI2 might enhance invasion of HCC by inducing epithelial–mesenchymal transition (EMT). Knockdown of MSI2 significantly decreased the invasion of HCC cells and changed the expression pattern of EMT markers. Moreover, immunohistochemistry assays of 149 HCC tissue specimens further confirmed this correlation. Taken together, the results of our study demonstrated that MSI2 correlates with EMT and has the potential to be a new predictive biomarker of HCC prognosis and invasion to help guide diagnosis and treatment of post-operative HCC patients.
Highlights
Hepatocellular carcinoma is one of the most common highly invasive malignant tumours associated with high recurrence incidence and poor prognosis [1, 2]
We observed that MSI1 was primarily localized in the cytoplasm, whereas MSI2 was primarily localized in the nucleus
We detected high expression of MSI1 in 56/149 (37.6%) hepatocellular carcinoma (HCC) tissues, compared with only 8/149 (5.3%) adjacent non-tumourous tissues (P < 0.001; Fig. 1A), whereas high expression of MSI2 was detected in 73/149 HCC tissues, compared with 12/149 adjacent non-tumourous tissues (P < 0.001; Fig. 1C)
Summary
Hepatocellular carcinoma is one of the most common highly invasive malignant tumours associated with high recurrence incidence and poor prognosis [1, 2]. Because of the underlying liver disease and the common resistance of HCC to existing antineoplastic agents, the efficacy of chemotherapy to HCC remains inadequate for a large number of patients [3,4,5]. Two members have been identified far: MSI1 and MSI2. These two genes exhibit a high degree of sequence similarity [11]. The literature suggests that these genes can take part in post-transcriptional regulation via a 2013 The Authors
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