Increased expression of FOXD1 is associated with cervical node metastasis and unfavorable prognosis in oral squamous cell carcinoma

Abstract

Background Previous studies suggest that FOXD1 is involved in tumorigenesis and closely related to the patients’ poor outcome in human cancer. However, its expression pattern in primary oral squamous cell carcinoma (OSCC) remains uncovered. In this study, we tried to explore the expression pattern of FOXD1 and its clinicopathological significance in primary OSCC. Methods Data mining and analysis on FOXD1 mRNA expression in OSCC samples were performed using publicly available databases. Its protein expression was supervised by immunohistochemistry in a retrospective cohort containing 58 primary OSCC samples. Furthermore, the potential associations between FOXD1 expression and various clinicopathological characteristics and patients’ survival were further investigated. Results Bioinformatic analysis indicated that FOXD1 mRNA abundance was obviously up‐regulated in OSCC cohorts. Immunohistochemical staining results showed that FOXD1 protein was significantly up‐regulated in OSCC specimens as compared to normal counterparts and its aberrant up‐regulation was remarkably related to cervical lymph node metastasis (P = .0198) and decreased overall survival (P = .0281) and disease‐free survival (P = .0312). Both univariate and multivariate Cox regression analysis further revealed the expression pattern of FOXD1 as an independent prognostic factor for overall survival of patients. Conclusion Taken together, these findings indicate that the aberrant up‐regulation of FOXD1 is related to cervical node metastasis and unfavorable prognosis in OSCC and it also may play a key role during OSCC tumorigenesis and regard as a novel diagnostic and prognostic biomarker for OSCC.

FOXD1 promotes EMT and cell stemness of oral squamous cell carcinoma by transcriptional activation of SNAI2

“…Therefore, finding genes that are crucial for tumor progression may provide new therapeutic targets for OSCC. Recent studies have demonstrated that upregulated FOXD1 is related to the metastasis status and adverse clinical outcomes of OSCC [ 10 ]. In addition, FOXD1-AS1 can enhance the proliferation and decrease the apoptosis of nasopharyngeal carcinoma by upregulating FOXD1 expression [ 21 ].…”

“…Li et al found that upregulated FOXD1 is related to the metastasis status and adverse clinical outcomes of OSCC [ 10 ]. However, they did not reveal the intrinsic mechanism of FOXD1 in regulating tumor progression.…”

“…For instance, Sun et al found that lncRNA NORAD promotes cell stemness and angiogenesis in liver cancer by regulating the miR-211-5p/FOXD1/VEGF-A axis [ 5 ]; Cheng et al found that FOXD1 can determine the renewal ability and tumorigenicity of glioma through transcriptional regulation of ALDH1A3 [ 9 ]. Recently, FOXD1 was found to be significantly highly expressed in OSCC tissues and related to overall survival, disease-free survival, and metastasis status [ 10 ]. Nevertheless, the function of FOXD1 in OSCC remains unclear.…”

FOXD1 Promotes EMT and Cell Stemness of Head and Neck Squamous Cell Carcinoma by Transcriptional Activation of SNAI2

“…Therefore, nding genes that are crucial for tumor progression may provide new therapeutic targets for HNSCC. Recent studies demonstrated that upregulated FOXD1 was related to the metastasis status and adverse clinical outcomes of oral squamous cell carcinoma [10]. Besides, FOXD1-AS1 could enhance the proliferation and decrease the apoptosis of nasopharyngeal carcinoma by upregulating FOXD1 expression [21].…”

“…For instance, Sun et al found LncRNA NORAD promoted cell stemness and angiogenesis of liver cancer via regulating miR-211-5p/FOXD1/VEGF-A axis [5]; Cheng et al found FOXD1 could determine the renewing ability and tumorigenicity of glioma through transcriptional regulation of ALDH1A3 [9]. Recently, FOXD1 was found to be signi cantly highly-expressed in OSCC tissues and related to overall survival, disease-free survival, and metastasis status [10]. Nevertheless, the function of FOXD1 in HNSCC remains unclear.…”