Gelsolin Promotes Cancer Progression by Regulating Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma and Correlates with a Poor Prognosis.

Yixi Zhang,Xue Liang,Xiangjun He,Jianwei Lin,Xiaojing Luo,Pei Feng,Shunjun Fu,Wen Deng,Hongjun Su,Kunpeng Liu

doi:10.1155/2020/1980368

Abstract

Gelsolin (GSN), a cytoskeletal protein, is frequently overexpressed in different cancers and promotes cell motility. The biological function of GSN in hepatocellular carcinoma (HCC) and its mechanism remain unclear. The expression of GSN was assessed in a cohort of 188 HCC patients. The effects of GSN on the migration and invasion of tumour cells were examined. Then, the role of GSN in tumour growth in vivo was determined by using a cancer metastasis assay. The possible mechanism by which GSN promotes HCC progression was explored. As a result, GSN was overexpressed in HCC tissues. High GSN expression was significantly correlated with late Edmondson grade, encapsulation, and multiple tumours. Patients with high GSN expression had worse overall survival (OS) and disease-free survival (DFS) than those with low GSN expression. GSN expression was identified as an independent risk factor in both OS (hazard risk (HR) = 1.620, 95% confidence interval (CI) = 1.105–2.373, P < 0.001) and DFS (HR = 1.744, 95% CI = 1.205–2.523, P=0.003). Moreover, GSN knockdown significantly inhibited the migration and invasion of HCC tumour cells, while GSN overexpression attenuated these effects by regulating epithelial-mesenchymal transition (EMT) In conclusion, GSN promotes cancer progression and is associated with a poor prognosis in HCC patients. GSN promotes HCC progression by regulating EMT.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common cancers and the fourth leading cause of cancer-related death worldwide [1]
Immunohistochemical analysis indicated that GSN mainly localizes within the cytoplasm of HCC tissues, in accord with previous reports, and the intensity of GSN-positive staining was markedly increased in HCC tissues compared with that in noncancerous tissues (Figure 1(c))
We evaluated the difference in GSN expression between metastatic HCC tissues and HCC tissues in situ (Figure 1(d))

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common cancers and the fourth leading cause of cancer-related death worldwide [1]. It has been reported that GSN is upregulated in both human HCC tissue and the hepatocellular cell line Hca-F, which has high lymphogenous metastatic potential [12, 13]. To further elucidate the role of GSN in HCC, we investigated GSN expression in human HCC and adjacent noncancerous tissues and the effect of GSN on invasion and migration in HCC cells. Our results showed that GSN promotes HCC cell migration and invasion in vitro, and the knockdown of GSN attenuates HCC metastasis in vivo, potentially by influencing the EMT process. Our results revealed that GSN promotes the migration and invasion of HCC cells in vitro, and the knockdown of GSN attenuates HCC metastasis in vivo by influencing the EMT process

Methods

Results

I-II III-IV

Discussion