DEFB4A is a potential prognostic biomarker for colorectal cancer

Wu,Qian; Wang,Dan; Zhang,Zhen; Wang,Yaping; Yu,Weina; Sun,Kai; Maimela,Nomathamsanqa Resegofetse; Sun,Zhenqiang; Liu,Jinbo; Yuan,Weitang; Zhang,Yi

doi:10.3892/ol.2020.11975

DEFB4A is a potential prognostic biomarker for colorectal cancer

Authors:
- Qian Wu
- Dan Wang
- Zhen Zhang
- Yaping Wang
- Weina Yu
- Kai Sun
- Nomathamsanqa Resegofetse Maimela
- Zhenqiang Sun
- Jinbo Liu
- Weitang Yuan
- Yi Zhang
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Affiliations: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Anorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: August 12, 2020 https://doi.org/10.3892/ol.2020.11975
Article Number: 114
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is the third leading cause of cancer‑associated mortality. The present study aimed to investigate novel biomarkers to predict prognosis and provide a theoretical basis for studies of the pathogenesis and the development of therapies for CRC. The present study compared mRNA expression levels of patients with CRC with short‑ and long‑term prognosis and of individuals with and without tumors in The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were identified via volcano plot and Venn diagram analysis. Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) were performed to identify the functions of the DEGs, and the DEGs were further verified using clinical CRC samples. A total of 10 DEGs were identified as candidate genes using the TCGA database, and four DEGs [defensin β 4A (DEFB4A), hyaluronan binding protein 2 (HABP2), oleoyl‑ACP hydrolase and TBC1 domain family member 3G] were associated with poor prognosis of patients with CRC. Two DEGs (DEFB4A and HABP2) were upregulated in tumor tissues of patients with CRC in the TCGA database. GO and GSEA analyses revealed that DEFB4A was highly associated with immunosuppression, participates in ‘myeloid leukocyte differentiation’, ‘leukocyte proliferation’ and ‘positive regulation of leukocyte‑mediated immunity’, and was positively correlated with CD11b, CD14, CD45, CD163 and IL17A. Furthermore, DEFB4A expression was significantly upregulated in patients with large tumors, advanced cancer stage, lymph node metastasis and liver metastasis. Survival analysis revealed that DEFB4A upregulation was associated with poor prognosis. DEFB4A gene knockdown experiments demonstrated that DEF4BA promotes cell migration. These results indicated that DEFB4A potentially promotes tumor growth by regulating immunosuppressive activity and provided novel insights into the diagnosis and treatment of CRC.

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