Largescale Transcriptomics Analysis Suggests Over-Expression of BGH3, MMP9 and PDIA3 in Oral Squamous Cell Carcinoma

PLoS One. 2016 Jan 8;11(1):e0146530. doi: 10.1371/journal.pone.0146530. eCollection 2016.

Abstract

Oral squamous cell carcinoma (OSCC) has been reported as the most prevalent cancer of the head and neck region, while early diagnosis remains challenging. Here we took a comprehensive bioinformatics study on microarray data of 326 OSCC clinical samples with control of 165 normal tissues. The cell interaction pathways of ECM-receptor interaction and focal adhesion were found to be significantly regulated in OSCC samples. Further analysis of the topological properties and expression consistency identified that three hub genes in the gene interaction network, MMP9, PDIA3 and BGH3, were consistently up-expressed in OSCC samples. When being validated on additional microarray datasets of 41 OSCC samples, the validation rate of over-expressed BGH3, MMP9, and PDIA3 reached 90%, 90% and 84% respectively. At last, immuno-histochemical assays were done to test the protein expression of the three genes on newly collected clinical samples of 35 OSCC, 20 samples of pre-OSCC stage, and 12 normal oral mucosa specimens. Their protein expression levels were also found to progressively increase from normal mucosa to pre-OSCC stage and further to OSCC (ANOVA p = 0.000), suggesting their key roles in OSCC pathogenesis. Based on above solid validation, we propose BGH3, MMP9 and PDIA3 might be further explored as potential biomarkers to aid OSCC diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cluster Analysis
  • Databases, Genetic
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Gene Expression Profiling*
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mouth Mucosa / metabolism
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism*
  • Protein Interaction Maps
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Extracellular Matrix Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • betaIG-H3 protein
  • Matrix Metalloproteinase 9
  • Protein Disulfide-Isomerases
  • PDIA3 protein, human

Grants and funding

This work was partly supported by the Fundamental Research Funds for the Central Universities to KLT, the Natural Science Foundation of Shanghai Science and Technology Commission (14ZR1443600), the guided project from Shanghai Science and Technology Commission (14411971800) and the Science Foundation of Shanghai Health Bureau (201440274) to YH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.