Oligoadenylate synthetases-like is a prognostic biomarker and therapeutic target in pancreatic ductal adenocarcinoma

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is fatal cancer that causes death. Early metastasis, resistance to chemotherapy, and lack of treatment contribute to a poor prognosis. Therefore, finding new therapeutic targets and biomarkers is a particularly urgent need to improve the survival of PDAC patients.Oligoadenylate synthetases-like (OASL), an antiviral enzyme produced by interferon (IFN), has been found to be associated with the occurrence and development of multiple cancers. However, its role in PDAC has been less well-studied. The value of OASL in PDAC was evaluated by bioinformatics and in vitro experiments.Methods: The expression of OASL was evaluated using the Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) online websites. The survival time was also calculated by GEPIA. The correlation between OASL messenger RNA (mRNA) expression and immune infiltration was analyzed by the Tumor Immune Estimation Resource (TIMER) database. Clinical characteristics were revealed by The Cancer Genome Atlas (TCGA) data. A nomogram and forest plot were constructed based on univariate and multivariate Cox regression. Cell experiments [western blot assays, 3-(4,5-dimethylathiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assays, transwell assays, flow cytometry assays] were used to verify the value of OASL in PDAC cells (Panc-1, Mia paca-2, and Aspc-1).Results: A higher expression of OASL was observed in PDAC (P<0.05). Patients with increased expression of OASL had worse overall survival (OS; P<0.05) and disease-specific survival (DSS; P<0.05). The expression of OASL was correlated with T stage (P=0.030) and N stage (P=0.004), radiation therapy (P=0.013), primary therapy outcome (P<0.001), residual tumor (P=0.028), and tumor location (P=0.004) by univariate analysis, which also confirmed that OASL was an independent prognostic factor. Moreover, OASL expression was positively associated with neutrophils. In vitro experiments indicated that knockdown of OASL inhibited cell viability and invasion while increasing apoptosis rate.Conclusions: High expression of OASL is associated with poor prognosis. Targeting OASL delays PDAC tumor progression in vitro. We highlight that OASL is a novel prognostic biomarker and therapeutic target of PDAC.

OASL knockdown inhibits the progression of stomach adenocarcinoma by regulating the mTORC1 signaling pathway

“…High OASL expression is associated with poor prognosis in patients with PDAC. 17 OASL may interact with ADAR to promote the proliferation and migration of breast cancer cells. 30 However, the effect of OASL on the progression of STAD has not been reported.…”

“…15 Furthermore, high OASL expression is associated with poor prognosis in breast cancer and pancreatic ductal adenocarcinoma. 16,17 However, the role of OASL in STAD remains elusive and requires further investigation.…”

“…Studies have shown that OAS family members may be the central genes involved in trastuzumab‐resistant gastric cancer 15 . Furthermore, high OASL expression is associated with poor prognosis in breast cancer and pancreatic ductal adenocarcinoma 16,17 . However, the role of OASL in STAD remains elusive and requires further investigation.…”

Progress of Actinidia chinensis Planch. root extract (acRoots) in cancer immunity

“…Research showed that OASL played an immune‐related role in cancers and viral infections. OASL −/− mice demonstrated increased IFN production and enhanced the cytotoxic function of CD8 + T cells and NK cells 74,75 . In addition, the PGE2/PTGES pathway plays a key role in inflammation 76 .…”

“…OASL −/− mice demonstrated increased IFN production and enhanced the cytotoxic function of CD8 + T cells and NK cells. 74,75 In addition, the PGE2/PTGES pathway plays a key role in inflammation. 76 Studies revealed that PTGES/PGE2 signaling protected tumour cells against T-cell cytotoxicity and recruited MDSCs to the tumour microenvironment.…”