The Clinical Significance of Forkhead Box M1 in Esophageal Squamous Cell Carcinoma Tissues: A Study Based on In-house Immunohistochemistry, RNA-sequencing, and Data Mining

Abstract

BackgroundEsophageal squamous cell carcinoma (ESCC) ranks the sixth in mortality rates in cancers due to a lack of a specific target of diagnosis and treatment in the early stages. Although Forkhead box M1 (FOXM1) has been reported to be differentially expressed in ESCC, its clinical role and function in ESCC remained unclarified.MethodsData from our hospital and public databases (n = 1906) were combined to estimate how FOXM1 overexpression showed its discriminatory ability between ESCC and non-ESCC esophageal tissues. Downstream targets of FOXM1 were predicted by using Cistrome database. Functional enrichment analyses were performed to explore the potential signaling pathways related to FOXM1 in ESCC. Based on the available clinical parameters, we investigated the prognosis potential of FOXM1 and its targets.ResultsThe pooled standard mean difference (SMD) for FOXM1 is 2.62 (95% CI: 2.08–3.16), indicating that FOXM1 is upregulated in ESCC. FOXM1 has an extremely high discrimination potential in ESCC because the area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) is 0.99 (95% CI: 0.97–0.99). A total of 168 downstream targets were identified, and nine hub genes were screened from them. We found that FOXM1 and its targets were significantly enriched in the cell cycle. Additionally, the correlation between FOXM1 and clinical parameters had not been observed, except for age.ConclusionsFOXM1 is upregulated in ESCC and has an extremely high discrimination potential in ESCC.