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Diagnostic and prognostic value of FOXD1 expression in head and neck squamous cell carcinoma.

ABSTRACT: FOXD1 has been reported to function as an oncogene in several types of cancer. This study evaluated the expression of FOXD1 and its role in head and neck squamous cell carcinoma (HNSCC). We mined the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases for expression profiles, clinical significance, and potential mechanisms of FOXD1in HNSCC. Our validation cohort consisted of FOXD1 mRNA expression in 162 paired HNSCC and adjacent normal tissues, as determined using quantitative real-time polymerase chain reaction. FOXD1 expression was upregulated in HNSCC in the public databases and in the validation cohort. The expression level of FOXD1 was associated with DNA amplification and methylation level. The areas under the curves (AUC) of TCGA cohort and the validation cohort were 0.855 and 0.843, respectively. Furthermore, higher FOXD1 expression was significantly associated with worse overall survival (hazard ratio [HR]: 1.849, 95% confidence interval [CI]: 1.280-2.670, P = 0.001) and a lower rate of recurrence-free survival (HR: 1.650, 95% CI: 1.058-2.575, P = 0.027) in patients with HNSCC. Moreover, gene set enrichment analysis showed that cases of HNSCC with FOXD1 overexpression were enriched in bladder cancer, cell cycle, DNA replication, glycosaminoglycan biosynthesis chondroitin sulfate, homologous recombination, glycan biosynthesis, nucleotide excision repair, p53 signaling pathway, pyrimidine metabolism, and spliceosome pathways. In summary, FOXD1 was significantly upregulated in HNSCC and was a good diagnostic biomarker and an independent predictor of poor survival and low rate of recurrence-free survival in patients with HNSCC.

SUBMITTER: Qiu S

PROVIDER: S-EPMC7778536 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue.MethodsWe analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan-Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene-drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results.ResultsCompared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion (p < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 (p < 0.0001). Gene-drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05).ConclusionsThe results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.

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Diagnostic and prognostic value of FOXD1 expression in head and neck squamous cell carcinoma.

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