Format

Send to

Choose Destination
Surg Oncol. 2019 Mar;28:180-189. doi: 10.1016/j.suronc.2018.12.003. Epub 2018 Dec 20.

Overexpression of CLN3 contributes to tumour progression and predicts poor prognosis in hepatocellular carcinoma.

Author information

1
Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, PR China; Yunnan Clinical Center for General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China; Yunnan Engineering Technology Centre for Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China.
2
Yunnan Clinical Center for General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China; Yunnan Engineering Technology Centre for Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China.
3
Yunnan Clinical Center for General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China; Yunnan Engineering Technology Centre for Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China. Electronic address: juehuayu@gmail.com.
4
Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, PR China; Yunnan Clinical Center for General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China; Yunnan Engineering Technology Centre for Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China. Electronic address: kunhuawang1@163.com.
5
Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, PR China; Yunnan Clinical Center for General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China; Yunnan Engineering Technology Centre for Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China. Electronic address: 1677546296@qq.com.

Abstract

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 μg/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.

KEYWORDS:

Biomarker; CLN3; Hepatocellular carcinoma; Prognosis; Tumour progression

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center