Determination of cytokine profile and associated genes of the signaling pathway in HNSCC

Abstract

Head and neck squamose cell carcinoma (HNSCC) is an aggressive group of tumors that are generally heterogeneous. Despite treatment advances, disease-free survival has not significantly improved. Therefore, it is of great importance to understand the molecular etiology of HNSCC and genetic alterations in the signal pathways in order to develop new therapeutic approaches. In this study, firstly we used a cytokine array to analyze the secretomes of HNSCC patients and healthy controls. In the next step, the results from the cytokine sequence were validated by qRT-PCR and western blot, including genes in the associated signaling pathway. In array analysis, the levels of EGF, IGF-1, IGFBP-1, and PDGFBB were significantly higher in patients than in the controls. The results of qRT-PCR analyses showed that expression levels of PDGFRB gene were significantly up-regulated (p = 0.006) and PTEN (p > 0.001) were significantly down-regulated in tumors compared with normal tissues. When groups (early vs. advanced) were compared, higher expression of IGFBP-1 was observed in the larynx (p = 0.045) and larynx + oral cavity tumors (p = 0.010) in an advanced stage. In western blot analysis, pEGFR, pIGF-IR, pIR-β, pPDGFRB, and pAKT levels were upregulated, and pPTEN was downregulated in tumors. Based on our observations, determining the interactions of EGFR, PDGFRB, IGF-1R and PTEN or the activation of each might represent a promising new and innovative treatment approach in HNSCC patients. It seems clear that, in most cancers, effective targeted therapy may be involved the blockade of each one or multiple targets.

Keywords:

• Head and neck squamose cell carcinoma
• cytokines
• receptors
• signal pathways

Acknowledgments

We would like to thank Prof. Dr. Ercan Kurar and Ph.D. student Fatma Secer Celik for their contribution.

Author contributions

AKY and TC designed the study, KO provided the tissues, AKY and AA performed the experiments, AKY interpreted the results of the experiments, MS made critical revisions to the manuscript.

Disclosurestatement

The authors declare that they have no competing interests.

Additional information

Funding

This study was supported by the Scientific Research Projects Foundation (BAP) of the Selcuk University of Turkey [Project No: #11102030].