Abstract
ObjectivesForkhead box D1, the core transcription factor member of FOX family, has gradually seen as a key cancerous regulatory. However, its expression and carcinogenicity in head and neck squamous cell carcinoma (HNSCC) have not been reported yet. This study was to investigate its expression pattern, clinicopathological significance and biological roles in HNSCC.MethodsHNSCC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to indicate the detailed expression pattern and outcome association of FOXD1, while Western Blot assay to detect FOXD1 level in a panel of HNSCC cell lines as well as immunocytochemistry to explore FOXD1 protein abundance and sublocation. Series of siRNA-mediated FOXD1 knock-down experiments to assess the proliferation, migration, invasion and anti- apoptosis ability after FOXD1 down-regulation. Bioinformatic analysis to find out which biological function and cancer-related pathways of FOXD1 associated genes involved in.ResultsFOXD1 mRNA was significantly overexpressed in TCGA-HNSCC, GSE6631, GSE12452, GSE25099 and GSE30784. Besides, IHC results shown that nuclear location FOXD1 protein was significantly higher in primary HNSCC specimens from cohort involved in this study. Also, FOXD1 abundance was significantly correlated with cervical node metastasis and poor over-all/disease-free survival after combination analysis with patient pathological information. siRNA-mediated FOXD1 knock-down significantly inhibited cell proliferation, migration and invasion and induced apoptosis in HNSCC cells. Further analysis of GSEA, GO and KEGG showed that FOXD1 expression was significantly associated with oncological function and cancer-related pathways.ConclusionsTaken together, our study implies that the potential oncogene, FOXD1, facilitates oncological behavior who can be identified as a brand-new HNSCC biomarker with diagnostic and prognostic significance.
Highlights
Malignant tumor in head and neck mainly occurrences in oral cavity, nasal cavity, sinus, throat and pharynx, which pathological type is mainly squamous cell carcinoma
Cell lines A panel of head and neck squamous cell carcinoma (HNSCC) cell lines including Cal27, Fadu, SCC9, SCC25, HN4, HN6 and human immortalized oral mucosa keratinocytes (HOK) were used in this study
Forkhead box D1 (FOXD1) mRNA is obviously up-regulated in public HNSCC sets Mounting study as well as pan-cancer analysis (Supplementary Figure1, downloaded from GEPIA2) have revealed that FOXD1 is overexpressed in a variety of cancers and has to do with unfavorable prognosis [11, 15]
Summary
Malignant tumor in head and neck mainly occurrences in oral cavity, nasal cavity, sinus, throat and pharynx, which pathological type is mainly squamous cell carcinoma (except thyroid tumor). It is the sixth most common malignant tumor in developed countries [1, 2]. According to the Global Cancer Statistics, there are over 550,000 new HNSCC patients and 300,000 HNSCC deaths worldwide every year [1, 3]. Clinical treatments of HNSCC patients has significantly been improved and improved the patient’s quality of life over the past decades, the prognosis of HNSCC is still unsatisfying, with the 5-year survival rate remaining around 50–60% [2, 3]. Exploring the potential molecular mechanisms of HNSC C will contribute to the development of molecular targeted therapies for this dreaded disease
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