J Cancer 2020; 11(19):5556-5567. doi:10.7150/jca.39888

Research Paper

Genome-wide RNA-sequencing dataset reveals the prognostic value and potential molecular mechanisms of lncRNA in non-homologous end joining pathway 1 in early stage Pancreatic Ductal Adenocarcinoma

Li-Ming Shang, Xi-Wen Liao, Guang-Zhi Zhu, Ke-Tuan Huang, Chuang-Ye Han, Cheng-Kun Yang, Xiang-Kun Wang, Xin Zhou, Hao Su, Xin-Ping Ye, Tao Peng

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

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Citation:
Shang LM, Liao XW, Zhu GZ, Huang KT, Han CY, Yang CK, Wang XK, Zhou X, Su H, Ye XP, Peng T. Genome-wide RNA-sequencing dataset reveals the prognostic value and potential molecular mechanisms of lncRNA in non-homologous end joining pathway 1 in early stage Pancreatic Ductal Adenocarcinoma. J Cancer 2020; 11(19):5556-5567. doi:10.7150/jca.39888. Available from http://www.jcancer.org/v11p5556.htm

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Abstract

Objective: Our current study is to explore the prognostic value and molecular mechanisms underlying the role of lncRNA in non-homologous end joining pathway 1 (LINP1) in early stage pancreatic ductal adenocarcinoma (PDAC).

Methods: Genome-wide RNA-seq datasets of 112 early stage PDAC patients were got from The Cancer Genome Atlas and analyzed using multiple online tools.

Results: Overall survival in high LINP1 expression patients was shorter than those with low expression (high-LINP1 vs. low-LINP1=481 vs. 592 days, log-rank P=0.0432). The multivariate Cox proportional hazard regression model suggested that high-LINP1 patients had a markedly higher risk of death than low-LINP1 patients (adjusted P=0.004, hazard ratio=2.214, 95% confidence interval=1.283-3.820). Analysis of genome-wide co-expressed genes, screening of differentially expressed genes, and gene set enrichment analysis indicated that LINP1 may be involved in the regulation of cell proliferation-, cell adhesion- and cell cycle-related biological processes in PDAC. Six small-molecule compounds including STOCK1N-35874, fenofibrate, exisulind, NU-1025, vinburnine, and doxylamine were identified as potential LINP1-targeted drugs for the treatment of PDAC.

Conclusions: Our study indicated that LINP1 may serve as a prognostic biomarker of early stage PDAC. Analysis of genome-wide datasets led to the elucidation of the underlying mechanisms and identified six potential targeted drugs for the treatment of early PDAC.

Keywords: lncRNA in non-homologous end joining pathway 1, pancreatic ductal adenocarcinoma, molecular mechanism, prognosis, The Cancer Genome Atlas