Shared genetic and epigenetic mechanisms between chronic periodontitis and oral squamous cell carcinoma

Simin Li; Xiangqiong Liu; Yu Zhou; Aneesha Acharya; Vuk Savkovic; Congling Xu; Ning Wu; Yupei Deng; Xianda Hu; Hanluo Li; Rainer Haak; Jana Schmidt; Wei Shang; Hongying Pan; Ren Shang; Yang Yu; Dirk Ziebolz; Gerhard Schmalz

doi:10.1016/j.oraloncology.2018.09.029

Shared genetic and epigenetic mechanisms between chronic periodontitis and oral squamous cell carcinoma

Oral Oncol. 2018 Nov:86:216-224. doi: 10.1016/j.oraloncology.2018.09.029. Epub 2018 Oct 3.

Authors

Simin Li¹, Xiangqiong Liu², Yu Zhou³, Aneesha Acharya⁴, Vuk Savkovic⁵, Congling Xu⁶, Ning Wu⁷, Yupei Deng⁸, Xianda Hu⁹, Hanluo Li⁵, Rainer Haak¹, Jana Schmidt¹, Wei Shang¹⁰, Hongying Pan¹¹, Ren Shang¹², Yang Yu¹³, Dirk Ziebolz¹⁴, Gerhard Schmalz¹

Affiliations

¹ Department of Cariology, Endodontology and Periodontology, University Leipzig, Liebigstr. 12, 04103 Leipzig, Germany.
² College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang Province, China; Shanghai Genomap Technologies, Kongjiang Road 1500, Yangpu District, Shanghai, China.
³ Department of Orthopedics, Civil Aviation Hospital of Shanghai, Shanghai, China.
⁴ Faculty of Dentistry, University of Hong Kong, Hong Kong, China; Dr D Y Patil Dental College and Hospital, Dr D Y Patil Vidyapeeth, Pimpri, Pune, India.
⁵ Saxon Incubator for Clinical Translation (SIKT), University of Leipzig, Germany.
⁶ State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
⁷ Ellen Institute for Dental Research and Education, Clinic of Laser Dentistry and Implantology, Arzbergstrasse 30, Steinbach-Hallenberg, Germany.
⁸ Shanghai Genomap Technologies, Kongjiang Road 1500, Yangpu District, Shanghai, China.
⁹ Beijing Tibetan Hospital, China Tibetology Research Center, 218 Anwaixiaoguanbeili Street, Chaoyang, Beijing 100029, China.
¹⁰ Department of Stomatology, The Heping Affiliated Hospital of Changzhi Medical College, Changzhi City, Shanxi Province, China.
¹¹ School of Dentistry, University of Michigan, USA.
¹² Department of Prosthodontics, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
¹³ Department of Periodontology, The Stomatology Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
¹⁴ Department of Cariology, Endodontology and Periodontology, University Leipzig, Liebigstr. 12, 04103 Leipzig, Germany. Electronic address: Dirk.Ziebolz@medizin.uni-leipzig.de.

PMID: 30409304
DOI: 10.1016/j.oraloncology.2018.09.029

Abstract

Objectives: To analyze bioinformatic datasets for detecting genetic and epigenetic mechanisms shared by chronic periodontitis (CP) and oral squamous cell carcinoma (OSCC).

Materials and methods: Datasets from GEO and TCGA databases reporting mRNAs, miRNAs or methylation expression in human CP and OSCC tissues were analyzed. Differential expression, functional enrichment and protein-protein interaction (PPI) network analyses were performed. Differentially expressed miRNAs (DEmiRNAs) and genes (DEG) in CP and OSCC were determined. DEmiRNA-target and DEmiRNA-DEG networks were constructed. Directly and indirectly interacting cross-talk genes were screened, and their prediction accuracy and association with OSCC prognosis was determined.

Results: 3 DE-miRNAs (miR-375, miR-3609 and miR-3652) expressed in both CP and OSCC critically regulated most DEGs. Among 12 directly interacting cross-talk genes, NCAPH was significantly related with the prognosis of OSCC. NR2F2 had highest differential expression in CP and OSCC. Among 4 cross-talk genes (FN1, MPPED1, NDEL1, and NR2F2) differentially expressed in CP, 3 (FN1, MPPED1, NDEL1) were also expressed in OSCC. Among 12 indirectly interacting cross-talk genes differentially expressed in OSCC, 3 genes (CDCA8, HIST1H3J, and RAD51) were significantly related to its prognosis. Significant pathways involved in CP and OSCC included: chemokine receptors, class I PI3K signaling events, epithelial-to-mesenchymal transition and signaling events by VEGFR1 and VEGFR2, EGF receptor (ErbB1).

Conclusion: Bioinformatic analysis of available datasets implicated 1 directly interacting cross-talk gene (NCAPH), 4 indirectly interacting cross-talk genes (NCAPH, NR2F2, FN1, and MPPED1) and 3 DE-miRNAs (hsa-miR-375, miR-3609 and miR-3652) as shared genetic and epigenetic expression patterns between CP and OSCC.

Keywords: Chronic periodontitis; Oral squamous cell carcinoma; Regulatory network; mRNA; miRNA.

Publication types

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

MeSH terms

Chronic Periodontitis / genetics*
Chronic Periodontitis / pathology
Computational Biology
DNA Methylation
Datasets as Topic
Epigenesis, Genetic*
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Humans
Mouth Neoplasms / genetics*
Mouth Neoplasms / pathology
Signal Transduction / genetics
Squamous Cell Carcinoma of Head and Neck / genetics*
Squamous Cell Carcinoma of Head and Neck / pathology