Journal
SURGICAL ONCOLOGY-OXFORD
Volume 28, Issue -, Pages 180-189Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.suronc.2018.12.003
Keywords
CLN3; Hepatocellular carcinoma; Tumour progression; Prognosis; Biomarker
Funding
- National Natural Science Foundation of China [81660094, 3171101074, 818170458, 81860306]
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The aberrant expression of ceroid-lipofuscinosis 3 (CLN3) has been reported in a variety of human malignancies. However, the role of CLN3 in the progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. In this study, we found that CLN3 was frequently upregulated in HCC clinical samples and HCC-derived cell lines and was significantly correlated with an APF serum level >= 20 mu g/L, a tumour size >= 5 cm, multiple tumours, and the absence of encapsulation. Kaplan-Meier showed that CLN3 upregulation predicted shorter recurrence-free survival (RFS) and overall survival (OS) time in HCC patients. Cox regression analysis revealed that CLN3 upregulation was an independent risk factor for RFS and OS. A functional study demonstrated that the knockdown of CLN3 expression profoundly suppressed the growth and metastasis of HCC cells both in vitro and in vivo. Mechanistic investigation revealed that the EGFR/PI3K/AKT pathway was essential for mediating CLN3 function. In conclusion, our results provide the first evidence that CLN3 contributes to tumour progression and metastasis and offer a potential prognostic predictor and therapeutic target for HCC.
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