DKK3 expression is correlated with poorer prognosis in head and neck squamous cell carcinoma: A bioinformatics study based on the TCGA database

Naoki Katase; Shin-Ichiro Nishimatsu; Akira Yamauchi; Shinji Okano; Shuichi Fujita

doi:10.1016/j.job.2023.09.002

DKK3 expression is correlated with poorer prognosis in head and neck squamous cell carcinoma: A bioinformatics study based on the TCGA database

J Oral Biosci. 2023 Dec;65(4):334-346. doi: 10.1016/j.job.2023.09.002. Epub 2023 Sep 15.

Authors

Naoki Katase¹, Shin-Ichiro Nishimatsu², Akira Yamauchi³, Shinji Okano⁴, Shuichi Fujita⁵

Affiliations

¹ Department of Oral Pathology, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-7-1, Nagasaki, Nagasaki, 852-8588, Japan. Electronic address: katase@nagasaki-u.ac.jp.
² Department of Natural Sciences, Kawasaki Medical School, Matsushima 577, Kurashiki, Okayama, 701-0192, Japan. Electronic address: shin@med.kawasaki-m.ac.jp.
³ Department of Biochemistry, Kawasaki Medical School, Matsushima 577, Kurashiki, Okayama, 701-0192, Japan. Electronic address: akiray@med.kawasaki-m.ac.jp.
⁴ Department of Pathology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan; Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan. Electronic address: okanos@nagasaki-u.ac.jp.
⁵ Department of Oral Pathology, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto 1-7-1, Nagasaki, Nagasaki, 852-8588, Japan. Electronic address: fujishu@nagasaki-u.ac.jp.

PMID: 37716425
DOI: 10.1016/j.job.2023.09.002

Abstract

Objective: We previously reported that dickkopf WNT signaling pathway inhibitor 3 (DKK3) expression is correlated with poorer prognosis in head and neck squamous cell carcinoma (HNSCC). Here we investigated DKK3 expression by using The Cancer Genome Atlas (TCGA) public database and bioinformatic analyses.

Methods: We used the RNA sequence data and divided the tumor samples into "DKK3-high" and "DKK3-low" groups according to median DKK3 expression. The correlations between DKK3 expression and the clinical data were investigated. Differentially expressed genes (DEGs) were detected using DESEq2 and analyzed by ShinyGO 0.77. A gene set enrichment analysis (GSEA) was also performed using GSEA software. The DEGs were also analyzed with TargetMine to establish the protein-protein interaction (PPI) network.

Results: DKK3 expression was significantly increased in cancer samples, and a high DKK3 expression was significantly associated with shorter overall survival. We identified 854 DEGs, including 284 up-regulated and 570 down-regulated. Functional enrichment analyses revealed several Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with extracellular matrix remodeling. The PPI network identified COL8A1, AGTR1, FN1, P4HA3, PDGFRB, and CEP126 as the key genes.

Conclusions: These results suggested the cancer-promoting ability of DKK3, the expression of which is a promising prognostic marker and therapeutic target for HNSCC.

Keywords: Bioinformatics; DKK3 protein, human; Head and neck squamous cell carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Computational Biology / methods
Databases, Genetic
Gene Expression Regulation, Neoplastic / genetics
Head and Neck Neoplasms* / genetics
Humans
Procollagen-Proline Dioxygenase / genetics
Prognosis
Squamous Cell Carcinoma of Head and Neck / genetics

Substances

P4HA3 protein, human
Procollagen-Proline Dioxygenase
DKK3 protein, human
Adaptor Proteins, Signal Transducing