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Network-based analysis of calcium-binding protein genes identifies Grp94 as a target in human oral carcinogenesis

H Nomura1, K Uzawa, Y Yamano

  • 1Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, Japan.

British Journal of Cancer
|August 30, 2007
PubMed

Insights

Glucose-regulated protein 94 kDa (Grp94) is overexpressed in oral squamous cell carcinomas (OSCCs) and oral premalignant lesions (OPLs). This Grp94 overexpression correlates with poorer survival, suggesting its potential as a diagnostic and prognostic biomarker for OSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Oral squamous cell carcinoma (OSCC) is a significant global health concern.
  • Understanding molecular alterations in OSCC is crucial for developing effective biomarkers.
  • Calcium (Ca2+)-binding proteins play roles in various cellular processes, including cancer development.

Purpose of the Study:

  • To identify differentially expressed Ca2+-binding protein genes in OSCC.
  • To investigate the role of glucose-regulated protein 94 kDa (Grp94) as a potential biomarker in OSCC and oral premalignant lesions (OPLs).

Main Methods:

  • Gene expression profiling of OSCC-derived cell lines and normal oral tissues.
  • Identification of differentially expressed Ca2+-binding protein genes and associated pathways.
  • Evaluation of Grp94 mRNA and protein expression using real-time quantitative reverse transcriptase-PCR and immunohistochemistry in cell lines, primary OSCCs, OPLs, and normal tissues.
  • Correlation analysis of Grp94 expression with clinical outcomes, specifically disease-free survival.

Main Results:

  • One hundred Ca2+-binding protein genes showed differential expression in OSCCs.
  • Glucose-regulated protein 94 kDa (Grp94) was significantly overexpressed in OSCC cell lines compared to normal oral epithelium (P<0.001).
  • Immunohistochemistry revealed high Grp94 expression in primary OSCCs and OPLs, with minimal to no expression in corresponding normal tissues.
  • Grp94 overexpression in primary tumors significantly correlated with poorer disease-free survival (P<0.001).

Conclusions:

  • Grp94 is significantly overexpressed in oral squamous cell carcinomas and oral premalignant lesions.
  • Grp94 protein expression levels are associated with poor disease-free survival in OSCC patients.
  • Grp94 shows potential as a novel diagnostic and prognostic biomarker for human OSCCs.

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