Transcriptomic analysis of Porphyromonas gingivalis‐infected head and neck cancer cells: Identification of PLAU as a candidate prognostic biomarker

Author:

Hamada Masakazu1ORCID,Inaba Hiroaki2,Nishiyama Kyoko1,Yoshida Sho2,Yura Yoshiaki1,Matsumoto‐Nakano Michiyo2,Uzawa Narikazu1

Affiliation:

1. Department of Oral & Maxillofacial Oncology and Surgery Osaka University Graduate School of Dentistry

2. Department of Pediatric Dentistry Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan

Abstract

AbstractPeriodontal disease is a risk factor for head and neck squamous cell carcinoma (HNSCC), and Porphyromonas gingivalis, a major periodontal pathogen, has been identified as a specific and potentially independent microbial factor that increases the risk of cancer mortality. Gene expression in HNSCC due to P. gingivalis infection and how changes in gene expression affect the prognosis of HNSCC patients are not clarified. When P. gingivalis was cultured with HNSCC cells, it efficiently adhered to these cells and enhanced their invasive ability. A transcriptome analysis of P. gingivalis ‐infected HNSCC cells showed that genes related to migration, including CCL20, CITED2, CTGF, C8orf44‐SGK3, DUSP10, EGR3, FUZ, HBEGF, IL1B, IL24, JUN, PLAU, PTGS2, P2RY1, SEMA7A, SGK1 and SIX2, were highly up‐ or down‐regulated. The expression of up‐regulated genes was examined using the expression data of HNSCC patients obtained from The Cancer Genome Atlas (TCGA) database, and the expression of 5 genes, including PLAU, was found to be higher in cancer tissue than in solid normal tissue. An analysis of protein–protein interactions revealed that these 5 genes formed a dense network. A Cox regression analysis showed that high PLAU expression levels were associated with a poor prognosis in patients with TCGA‐HNSCC. Furthermore, the prognostic impact correlated with tumour size and the presence or absence of lymph node metastasis. Collectively, these results suggest the potential of PLAU as a molecular prognostic marker in HNSCC patients. Further in vivo and in vitro studies are needed to verify the findings of this study.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

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