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

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机构: [a]Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, PR China [b]Yunnan Clinical Center for General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China [c]Yunnan Engineering Technology Centre for Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China
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关键词: CLN3 Hepatocellular carcinoma Tumour progression Prognosis Biomarker

摘要:
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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基金编号: No. 81660094, No. 3171101074, No. 818170458, and No. 81860306

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出版当年[2020]版:
大类 | 3 区 医学
小类 | 3 区 外科 4 区 肿瘤学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学 4 区 外科
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出版当年[2019]版:
Q2 SURGERY Q3 ONCOLOGY
最新[2023]版:
Q2 SURGERY Q3 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [a]Department of Gastrointestinal and Hernia Surgery, The First Affiliated Hospital of Kunming Medical University, PR China [b]Yunnan Clinical Center for General Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China [c]Yunnan Engineering Technology Centre for Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, PR China
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通讯作者:
通讯机构: [*1]Department of Gastrointestinal and Hernia Surgery and Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan Province, PR China. [*2]Department of Gastrointestinal and Hernia Surgery and Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan Province, PR China. [*3]Department of Gastrointestinal and Hernia Surgery and Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan Province, PR China
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