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

Shihong Chen; Zhijian Sun; Weizhu Zhao; Mingyang Meng; Wenyi Guo; Dong Wu; Qiang Shu; Jie Chai; Lei Wang

doi:10.21037/atm-21-6618

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

Ann Transl Med. 2022 Feb;10(3):138. doi: 10.21037/atm-21-6618.

Authors

Shihong Chen^#¹, Zhijian Sun^#^{2

3}, Weizhu Zhao⁴, Mingyang Meng⁵, Wenyi Guo¹, Dong Wu¹, Qiang Shu^{2

3}, Jie Chai⁶, Lei Wang¹

Affiliations

¹ Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Department of Rheumatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
³ Shandong Provincial Clinical Research Center for Immune Diseases and Gout, Qilu Hosptial, Jinan, China.
⁴ Department of Radiology, Cancer Hospital Affiliated to Shandong First Medical University, Shandong Cancer Hospital and Institute, Jinan, China.
⁵ Department of General Medicine, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
⁶ Department of Gastrointestinal Surgery, Cancer Hospital Affiliated to Shandong First Medical University, Shandong Cancer Hospital and Institute, Jinan, China.

^# Contributed equally.

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)-2,5-diphenyltetrazolium 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.

Keywords: Oligoadenylate synthetases-like (OASL); TCGA; immune infiltration; pancreatic ductal adenocarcinoma (PDAC); prognosis.