Actin gamma 1 is a critical regulator of pancreatic ductal adenocarcinoma

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of pancreatic cancers, which represents one of the most lethal malignancies with a 5-year overall survival less than 10%. Identifying molecular biomarkers is invaluable in helping to predict clinical outcomes and developing targeted chemotherapies. Actin gamma 1 (ACTG1) is a kind of actin isoform that exists in almost all cell types as a component of the cytoskeleton, thus mediating cell viability. Although there have been studies revealing the prognostic significance of ACTG1 in several malignancies such as glioblastoma and hepatocellular carcinoma, its involvement and function in pancreatic cancer needs to be elucidated. Methods: We retrospectively enrolled a cohort of PDAC patients after surgical resection (n = 149) and conducted immunohistochemistry experiments to explore the expression profile of ACTG1. Univariate and multivariate analyses were performed to investigate the clinical relevance of ACTG1. The functional role of ACTG1 in PDAC progression was further validated via both in vitro and in vivo studies. Results: ACTG1 presented a higher expression in PDAC tissues than in nontumorous pancreatic tissues. ACTG1 level positively correlated with tumor stage, implying its potential role as a tumor promoter. Univariate and multivariate analyses identified that patients with lower ACTG1 showed a better overall survival compared to those with higher ACTG1 expression. Cellular and xenograft experiments confirmed the role of ACTG1 on facilitating tumor proliferation both in vitro and in vivo. Conclusions: Our study revealed a pro-oncogenic role of ACTG1 in PDAC, which may help predict prognosis and serve as a novel therapeutic target.

Keywords

• actg1
• pancreatic adenocarcinoma
• prognosis
• proliferation