Abstract
Objectives Previous experiments have shown that growth factor receptors play important role in tumor proliferation, metastasis, and therapeutic effect of chemotherapeutic drugs. At the same time, forkhead box D1 (FOXD1) plays an important role in a variety of signal transmission, but its expression profile was known little about head and neck cancer. The purpose of this experiment was to explore the regulation of FOXD1 on the tumor progression of head and neck cancer and to explore the correlation of FOXD1 on the expression of growth factor receptors (EGFR). Methods The bioinformatics online database analyzed the expression of FOXD1 and EGFR in tumor tissues and nontumor tissues. Real-time quantitative PCR was used to detect the FOXD1 and EGFR expression in 45 tumor tissues and 15 nontumor tissues. The plasmid was used to construct FOXD1 overexpressing head and neck squamous cell cancer lines and observe the clonal formation and invasion of tumor cells under the intervention of EGFR-specific antibody—cetuximab. Results The expression of FOXD1 and EGFR in tumor tissues was higher than that in nontumor tissues. The higher expression of FOXD1 and EGFR was not conducive to the prognosis of patients. The expression of FOXD1 and EGFR was positively correlated, and immunohistochemical analysis showed the high expression of FOXD1 and EGFR has close relation to the advanced stage of the tumor. In vitro cell experiments proved that overexpression of FOXD1 can partially offset the cloning ability of cetuximab on head and neck tumor cells. Conclusion FOXD1 has an important regulatory role in the progression of head and neck cancer, and its abnormally high expression was not conducive to the prognosis of cancer patients. FOXD1 can regulate the expression of growth factor receptors in head and neck cancer, which provides a new idea for the better use of tumor growth factor receptor-specific antibodies for collaborative therapy.
Highlights
Head and neck cancer has a high mortality rate, usually as high as 50–80% within 24 months after diagnosis [1]. e patient’s quality of life is severely impaired, usually accompanied by disturbances in swallowing, daily speech, chewing, and facial expressions [2]. erapies currently approved by the FDA for the treatment of advanced metastatic head and neck cancer include cetuximab, an antibody that blocks the receptor tyrosine kinase (RTK) epithelial growth factor receptor (EGFR), and it is usually combined with other radiotherapy drugs for the treatment of advanced locally metastatic head and neck cancer [3, 4]
It can be clearly found that the expression levels of forkhead box D1 (FOXD1) and EGFR in tumor tissues are higher than those in nontumor tissues. ese experimental results can fully explain the high expression of FOXD1 and EGFR in head and neck cancer
Patients with high EGFR expression have a lower survival time compared with patients with low EGFR expression. rough immunohistochemical analysis (Figure 2(d)), we can clearly find that the expression levels of FOXD1 and EGFR in the T3 stage of advanced tumor tissues are higher than the expression levels of early T1. rough the above analysis, we can clearly draw the following conclusions: the expression levels of FOXD1 and EGFR have a very important impact on the survival of patients with head and neck cancer, and abnormally high expression is not conducive to the prognosis of patients
Summary
Head and neck cancer has a high mortality rate, usually as high as 50–80% within 24 months after diagnosis [1]. e patient’s quality of life is severely impaired, usually accompanied by disturbances in swallowing, daily speech, chewing, and facial expressions [2]. erapies currently approved by the FDA for the treatment of advanced metastatic head and neck cancer include cetuximab, an antibody that blocks the receptor tyrosine kinase (RTK) epithelial growth factor receptor (EGFR), and it is usually combined with other radiotherapy drugs for the treatment of advanced locally metastatic head and neck cancer [3, 4]. Head and neck cancer has a high mortality rate, usually as high as 50–80% within 24 months after diagnosis [1]. Erapies currently approved by the FDA for the treatment of advanced metastatic head and neck cancer include cetuximab, an antibody that blocks the receptor tyrosine kinase (RTK) epithelial growth factor receptor (EGFR), and it is usually combined with other radiotherapy drugs for the treatment of advanced locally metastatic head and neck cancer [3, 4]. Cetuximab can significantly prolong the median overall survival of head and neck cancer patients, the clinical remission rate was limited to late local disease with a course of about 10 months or metastatic disease with a course of 2-3 months [5,6,7,8]. E forkhead box (FOX) family, composed of proteins that share related winged helix-turn-helix DNA binding motifs, belongs to the “winged helix” superfamily [13]. FOXD1 dysfunction has been linked to different pathologies, which constitutes diagnostic biomarker and becomes a promising target for future treatment [14]
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