Abstract
Forkhead box D1 (FOXD1) is a new member of FOX transcription factor family. FOXD1 has demonstrated multilevel roles during normal development, and several diseases’ pathogenesis. However, little is known about the role of FOXD1 in the progression of head and neck squamous cancer (HNSC). In the present study, we analyzed FOXD1 expression pattern using The Cancer Genome Atlas (TCGA) dataset, Gene Expression Omnibus (GEO) datasets, HNSC cell lines, and HNSC tissues. Then, we analyzed the correlation between FOXD1 expression and clinical characteristics, and evaluated the prognostic value of FOXD1 in HNSC. Moreover, we assessed the relationship between FOXD1 expression and tumor microenvironment (TME) and immune cell infiltration using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and Cell-type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) algorithms. Finally, we predicted the FOXD1-related biological processes (BPs) and signal pathways. FOXD1 was up-regulated in HNSC tissues in TCGA datasets, validated by GEO datasets, HNSC cell lines and HNSC tissues. FOXD1 expression was significantly associated with tumor site and HPV infection. Univariate and multivariate Cox regression analyses showed that FOXD1 expression was an independent prognostic factor. Moreover, we found that the proportions of naïve B cells, plasma cells, and resting dendritic cells (DCs) were negatively correlated with FOXD1 expression, otherwise, the proportion of activated mast cells was positively correlated with FOXD1 expression using CIBERSORT algorithm. Gene Set Enrichment Analyses (GSEAs) revealed that FOXD1 was mainly involved in cancer-related signaling pathway and metabolism-related pathways. FOXD1 was a potential oncogene, and might represent an indicator for predicting overall survival (OS) of HNSC patients. Moreover, many cancer-related pathways and metabolism-related processes may be regulated by FOXD1.
Highlights
Head and neck cancer (HNC) is an aggressive malignant tumor arising in oral cavity, oropharynx, hypopharynx and larynx, representing the sixth most common cancer and fifth leading cause of cancer-related deaths worldwide [1]
Forkhead box D1 (FOXD1) expression was up-regulated in breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), lung squamous cell carcinoma (LUSC), prostate adenocarcinoma (PRAD), and stomach adenocarcinoma (STAD)
FOXD1 expression was down-regulated in kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), thyroid carcinoma (THCA), and uterine corpus endometrial carcinoma (UCEC)
Summary
Head and neck cancer (HNC) is an aggressive malignant tumor arising in oral cavity, oropharynx, hypopharynx and larynx, representing the sixth most common cancer and fifth leading cause of cancer-related deaths worldwide [1]. The vast majority of HNC are squamous carcinomas (head and neck squamous cancer, HNSC), accounting for more than 90% of HNC. FOXD1 has demonstrated multilevel roles during normal development, adult physiology, and several diseases’ pathogenesis. Previous studies reported that FOXD1 was a mediator and indicator in the process of cell programming, especially in kidney development [3–5]. Herrera et al reported that foxd plays a dual role in retinal ganglion cell axon migration through the optic chiasm [6]. Accumulating evidence has demonstrated that FOXD1 is implicated in the carcinogenesis, including lung cancer [7], colorectal cancer [8], ovarian cancer [9], breast cancer [10], nasopharyngeal carcinoma [11], gastric cancer [12], and prostate cancer [13]. Little is known about the role of FOXD1 in the progression of HNSC
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