J Cancer 2021; 12(7):2122-2139. doi:10.7150/jca.46084 This issue

Research Paper

UXT antisense RNA 1 sever as a novel prognostic long non-coding RNA in early stage pancreatic ductal adenocarcinoma patients after receiving pancreaticoduodenectomy

Xiwen Liao1, Rui Huang2, Xiangkun Wang1, Ketuan Huang1, Chengkun Yang1, Xin Zhou1, Chuangye Han1, Hao Su1, Xinping Ye1, Kang Liu3, Guangzhi Zhu1, Tao Peng1✉

1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
2. Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
3. Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

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Citation:
Liao X, Huang R, Wang X, Huang K, Yang C, Zhou X, Han C, Su H, Ye X, Liu K, Zhu G, Peng T. UXT antisense RNA 1 sever as a novel prognostic long non-coding RNA in early stage pancreatic ductal adenocarcinoma patients after receiving pancreaticoduodenectomy. J Cancer 2021; 12(7):2122-2139. doi:10.7150/jca.46084. Available from https://www.jcancer.org/v12p2122.htm

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Abstract

Graphic abstract

Objective: The principal objective of this project was to investigate the prognostic value of UXT antisense RNA 1 (UXT-AS1) in pancreatic ductal adenocarcinoma (PDAC), as well as its biological function mechanisms and the screening of targeted drugs using The Cancer Genome Atlas (TCGA) PDAC genome-wide RNA sequencing (RNA-seq) dataset.

Methods: We used TCGA 112 early stage PDAC patients to screen the prognostic value of UXT-AS1. Biological functions and mechanisms of UXT-AS1 were investigated by co-expression analysis, differentially expressed genes (DEGs) and gene set enrichment analysis, while targeted drug screening was investigated by connectivity Map (CMap).

Results: By analyzing the dataset from TCGA cohort, we found that UXT-AS1 was significantly up-regulated in pancreatic cancer tissues. Multivariate survival analysis demonstrated that PDAC patients with high UXT-AS1 expression had an unfavourable prognosis (adjusted P=0.033, HR=1.830, 95%CI=1.051-3.188). Genome-wide co-expression analysis and gene set enrichment analysis suggested that UXT-AS1 may act as a pivotal part in PDAC by participating in nuclear factor kappa beta, regulation of tumor necrosis factor, cell adhesion, T cell receptor signaling pathway, and numerous immune-related biological processes and signaling pathways. Functional enrichment analysis of DEGs between high- and low-UXT-AS1 expression groups suggested that these DEGs were significant enriched in B cell receptor complex, response to drug chemical carcinogenesis and drug metabolism-cytochrome P450. CMap analysis revealed that quipazine and terazosin may be targeted drugs for UXT-AS1 in PDAC.

Conclusion: Our current study has identified UXT-AS1 as a novel biomarker for the prognosis of early stage PDAC. We also clarified its biological functional mechanisms and identified two targeted drugs of UXT-AS1 in PDAC.

Keywords: UXT antisense RNA 1, The Cancer Genome Atlas, pancreatic ductal adenocarcinoma, pancreaticoduodenectomy, prognosis