J Cancer 2019; 10(18):4208-4216. doi:10.7150/jca.33457

Research Paper

The Role of Upregulated DDX11 as A Potential Prognostic and Diagnostic Biomarker in Lung Adenocarcinoma

Jianhao Li1,2*, Liwen Liu1,2*, Xin Liu1,2, Penglin Xu2, Qiuyue Hu1,2, Yan Yu1,2✉

1. Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
2. Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
*These authors contributed equally to this work.

Abstract

Background: Lung adenocarcinoma (ADC) is the main cause of cancer-related mortality in lung cancer patients. DEAD/DEAH box helicase 11 (DDX11) was previously shown to be dysregulated and to exert oncogenic activity in cancer. However, the diagnostic value and clinical significance of DDX11 in ADC remain unknown.

Methods: A total of 513 ADC and 59 normal tissue samples were obtained from The Cancer Genome Atlas (TCGA) database, and the mRNA expression level of DDX11 in ADC was evaluated. Additionally, a meta-analysis of 7 ADC cohorts from the Gene Expression Omnibus (GEO) database was conducted to validate the DDX11 expression pattern. Moreover, receiver operating characteristic (ROC) curve analysis was used to identify the diagnostic power of DDX11 in ADC. A tissue microarray (TMA) comprising 86 ADC specimens and their adjacent normal specimens was applied to indicate DDX11 protein expression status. In addition, Kaplan-Meier and Cox regression analyses were conducted to validate the prognostic value of DDX11 in ADC. Finally, the molecular mechanism of DDX11 action in ADC was predicted by gene set enrichment analysis (GSEA).

Results: DDX11 was upregulated in ADC tissues and was associated with worse overall survival (OS). ROC curves of DDX11 showed high values for diagnosis. Additionally, DDX11 expression has remarkable correlations with DNA replication and the cell cycle G1-S phase pathway. Consistently, it was associated with cell cycle genes, such as CCNA2, CCNB1, CCNC, CCND1, CCNE1, CDK2, CDK4 and CDK6. Moreover, high CCNA2, CCNB1, CCNE1 and CDK6 expression in ADC patients predicted worse OS and progression-free survival (PFS).

Conclusion: DDX11 was significantly upregulated and predicted poor prognosis in ADC. This gene might serve as a potential novel prognostic and diagnostic biomarker for ADC.

Keywords: DDX11, lung adenocarcinoma, diagnosis, proliferation, cell cycle

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How to cite this article:
Li J, Liu L, Liu X, Xu P, Hu Q, Yu Y. The Role of Upregulated DDX11 as A Potential Prognostic and Diagnostic Biomarker in Lung Adenocarcinoma. J Cancer 2019; 10(18):4208-4216. doi:10.7150/jca.33457. Available from http://www.jcancer.org/v10p4208.htm