Abstract
BackgroundSquamous 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.MethodsTo 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.ResultsWe 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.ConclusionsTaken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients.
Highlights
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
We evaluated the prognostic potential of 16 putative prognostic biomarkers (AZGP1, BTG2, CBX2, CNTNAP2, DNALI1, LOC389033, NME5, PIP, S100A8, SCUBE2, SERPINA11, STC2, STK32B, SUSD3, UBE2C, and WHSC1L1) previously identified in breast carcinoma using oral squamous cell carcinoma [14,15]
Others, have been able to show that AZGP1, S100A8, and STK32B, as well as CNTNAP2 are associated with the basal-like phenotype and lymph node metastasis, respectively [15,16,17]
Summary
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. Additional evidence of shared cellular processes was found between breast carcinoma and oral squamous cell carcinoma, i.e. mechanisms for tumor lymphangiogenesis and metastasis to the regional lymph nodes as well as HER2/ neu polymorphisms [11,12] These findings suggest that cancers derived from different sites of origin may perturb common signaling pathways and thereby display similar tumor characteristics [13]. To test this hypothesis, we evaluated the prognostic potential of 16 putative prognostic biomarkers (AZGP1, BTG2, CBX2, CNTNAP2, DNALI1, LOC389033, NME5, PIP, S100A8, SCUBE2, SERPINA11, STC2, STK32B, SUSD3, UBE2C, and WHSC1L1) previously identified in breast carcinoma using oral squamous cell carcinoma [14,15]. Others, have been able to show that AZGP1, S100A8, and STK32B, as well as CNTNAP2 are associated with the basal-like phenotype and lymph node metastasis, respectively [15,16,17]
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