Abstract
Purpose
As a type of cancer with the highest morbidity and mortality, lung squamous cell carcinoma (LUSC) has a very poor prognosis. Long-non-coding RNA (lncRNA) has recently attracted attentions because it can play the role of competing endogenous RNA (ceRNA) to inhibit microRNA (miRNA) functions. In this study, we aimed to find prognosis-related lncRNAs, miRNAs and mRNAs and construct a prognosis-related ceRNA network.
Methods
The original LUSC RNA-sequencing data and miRNA profiles data were downloaded from the cancer genome atlas (TCGA) database. Differentially expressed lncRNAs, miRNAs and mRNAs were then identified between patients with lymph node metastasis and no lymph node metastasis. Univariate Cox regression analysis was performed to find the survival-associated lncRNAs, miRNAs and mRNAs. Subsequently, prognostic-related ceRNA network was established. By multivariate Cox regression analysis, three lncRNA signatures and three mRNA signatures were developed and used for predicting LUSC patients’ survival.
Results
A total of 224 lncRNAs, 160 miRNAs, 913 mRNAs were identified between samples with lymph node metastasis and no lymph node metastasis. Univariate Cox regression analysis showed that, among them, 28 lncRNAs, 8 miRNAs, 105 mRNAs were significantly associated with patients’ overall survival time. Further pathway and enrichment analysis suggested that these mRNAs were associated with the regulation of transmembrane transport, regulation of blood circulation, plasma lipoprotein particle organization. Then we constructed a survival-related ceRNA network including 9 lncRNAs, 8 miRNAs and 23 mRNAs. Additionally, a multivariate Cox regression analysis demonstrated that three lncRNAs (AL161431.1, LINC02389, APCDD1L.DT) and three mRNAs (KLK6, SLITRK5, CCDC177) had a significant prognostic value. Risk score indicated that lncRNA signature and mRNA signature could independently predict overall survival in LUSC patients.
Conclusion
The current study provided a better understanding of the ceRNA network in the progression of LUSC and laid a theoretical foundation for LUSC prognosis.
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Acknowledgements
The authors sincerely thank all participants involved in this study.
Funding
This study was supported by The National Science Foundation for Young Scientists of China (Grant No. 81802415 to YZ), Shandong Provincial Natural Science Foundation (Grant No. ZR2018PH025 to YZ), The Doctoral Scientific Fund Project of the Affiliated Hospital of Qingdao University (Grant No. 2796 to QJ), Clinical Medicine + X Project, Medical College, Qingdao University.
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QJ and YZ designed and supervised the study. SM, XL and HZ analyzed the data and wrote the original draft. SZ, YY, SY edited draft. All authors have read and approved the final manuscript.
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Ju, Q., Zhao, Yj., Ma, S. et al. Genome-wide analysis of prognostic-related lncRNAs, miRNAs and mRNAs forming a competing endogenous RNA network in lung squamous cell carcinoma. J Cancer Res Clin Oncol 146, 1711–1723 (2020). https://doi.org/10.1007/s00432-020-03224-8
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DOI: https://doi.org/10.1007/s00432-020-03224-8