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Open Access Research article

Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

Toshima Z Parris1*, Luaay Aziz2*, Anikó Kovács3, Shahin Hajizadeh3, Szilárd Nemes45, May Semaan1, Chang Yan Chen16, Per Karlsson1 and Khalil Helou1

Author Affiliations

1 Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

2 Department of Otolaryngology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

3 Department of Clinical Pathology and Cytology, Sahlgrenska University Hospital, Gothenburg, Sweden

4 Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden

5 Regional Cancer Center (West), Western Sweden Health Care Region, Sahlgrenska University Hospital, Gothenburg, Sweden

6 Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

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BMC Cancer 2014, 14:324  doi:10.1186/1471-2407-14-324

Published: 7 May 2014

Abstract

Background

Squamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness.

Methods

To extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models.

Results

We found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively.

Conclusions

Taken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients.

Keywords:
Oral squamous cell carcinoma; Outcome prediction; Molecular biomarker; Immunohistochemistry; Model validation