iLIVER | CCL16通过影响CK19表型来抑制肝癌的肿瘤增殖和转移

中文题目：

代谢综合征与非酒精性脂肪性肝炎患者明显的肝纤维化和脂肪变性有关

英文题目：

CCL16 inhibits tumor proliferation and metastasis in HCC by impacting CK19 phenotype

作者及单位：

Huigang Li ^a 1, Jianyong Zhuo ^b 1, Peiru Zhang ^c 1, Jinyan Chen ^a 1, Zuyuan Lin ^a d, Xudong Yang ^e, Ruijie Zhao ^a, Chenghao Cao ^a, Wei Shen ^a,Chiyu He ^a, Hao Chen ^a, Ting Lv ^d, Xuyong Wei ^f g, Shusen Zheng ^g h i, Xiao Xu ^f g j, Di Lu ^f g

a

Zhejiang University School of Medicine, Hangzhou 310058, China

b

Department of Hepatobiliary and Pancreatic Surgery, Hangzhou First People’s Hospital, Hangzhou 310006, China

c

The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310000, China

d

Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310000, China

e

Hangzhou Normal University, Hangzhou 310000, China

f

Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou 310014, China

g

NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China

h

Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China

i

Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou 310000, China

j

Institute of Translational Medicine, Zhejiang University, Hangzhou 310000, China

如何引用：

Huigang Li, Jianyong Zhuo, Peiru Zhang, et al. CCL16 inhibits tumor proliferation and metastasis in HCC by impacting CK19 phenotype,iLIVER;3(2):100096.

https://doi.org/10.1016/j.iliver.2024.100096.

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Hepatocellular carcinoma

Cytokeratin 19

C–C motif chemokine ligand 16

Mast cells

Prognosis

Background and aims：

Cytokeratin 19–positive (CK19+) hepatocellular carcinoma (HCC) is an aggressive subtype with poor outcomes. The initiation and development of CK19+ HCC in the background of liver cirrhosis remains unclear. This study investigated the role of the cirrhosis-related gene C–C motif chemokine ligand 16 (CCL16) in the development of CK19+ HCC.

Methods：

Datasets from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) were analyzed to screen and validate the genes associated with CK19+ HCC. A total of 102 HCC patients were included for tissue microarray analysis. Gain-of-function experiments were conducted to investigate the biological functions of CCL16. CIBERSORT was used to investigate the correlation of CCL16 and immune infiltration.

Results：

GEO dataset analysis showed that CK19+ HCC had lower expression of CCL16. In both TCGA dataset and our HCC cohort, CCL16 expression was negatively correlated with CK19 expression (P < 0.05) and its expression was higher in para-tumor than tumor tissues (P < 0.001). Moreover, low CCL16 expression was related to advanced stage and poor overall survival (P < 0.05). CCL16 overexpression downregulated CK19 expression and impacted the sphere formation ability of HCC cells. Overexpression of CCL16 inhibited the cell proliferation, migration, and invasion of HCC cell lines. Immune analysis showed HCC with high CCL16 expression had more infiltration of mast cells. HCC patients with both low CCL16 expression and low mast cells had the worst prognosis (P < 0.001).

Conclusion：

Our data indicated that CCL16 downregulated the expression of CK19 and inhibited the malignant phenotype of HCC.