Tight correlation between FoxM1 and FoxP3+ Tregs in gastric cancer and their clinical significance

Abstract

The aim of the present study was to investigate the expression of Forkhead box transcription M1 (FoxM1) and Forkhead box transcription P3 (FoxP3) in gastric cancer tissues in order to reveal any correlation between FoxM1, FoxP3 and clinicopathological parameters. Their clinical significance in gastric cancer was also investigated. Immunohistochemistry was used to detect the expression of FoxM1 and FoxP3 in gastric cancer and para-cancer tissues. The clinical significance of FoxM1 and FoxP3 in gastric cancer was explored, and the association between FoxM1 and FoxP3 was further analyzed. As a result, the overexpression of FoxM1 and FoxP3 was evident in gastric cancer (P < 0.001). FoxM1 overexpression was showed to be correlated with late AJCC stage (P = 0.025), while positive tumoral FoxP3 expression was associated with deeper invasion (P = 0.020), lymph node metastasis (P = 0.019) and later AJCC stage (P = 0.024). Overexpression of FoxM1 or FoxP3 was revealed to be negative prognostic factors for survival duration (P < 0.05), whereas only FoxM1 was shown to be independently associated with prognosisin gastric cancer after multivariate analysis (P = 0.020). A significant and positive correlation between FoxM1 and FoxP3 expressions was finally confirmed (P = 0.001). This significantly positive correlation between FoxM1 and FoxP3 prompts that FoxM1 may induce immune inhibition by recruiting FoxP3+ Tregs, leading to the progression of carcinogenesis, invasion and metastasis.

Prognostic biomarkers and therapeutic targets in oral squamous cell carcinoma: a study based on cross-database analysis

“…The functions of regulatory T cells (Tregs) in immune regulation is well known, and much is being made of their potential for PDCD1 based therapy [ 64 ]. Recently, researchers found that the expression of FOXM1 was positive correlated with FOXP3 (the specific molecular marker of Tregs) and FOXM1 may induce immune suppression via recruiting FOXP3 positive Tregs in cancer therapy [ 65 ]. These results highlight the therapeutic potential of FOXM1 in OSCC.…”

Forkhead box M1 recruits FoxP3+ Treg cells to induce immune escape in hilar cholangiocarcinoma

“…In this study, we found that FoxP3 was upregulated in HCCA cells and FoxM1 bound to the FoxP3 promoter region to promote FoxP3 transcription. Similarly, both FoxM1 and FoxP3 were strongly expressed in gastric cancer, resulting in tumor metastasis, immune escape, and poor prognosis 21 . Our experiments revealed that the silencing of FoxP3 expression led to decreased levels of TGF‐β and IL‐6 as well as inhibited HCCA cell migration and invasion in case of adding Treg cells.…”

FOXM1 Inhibition in Ovarian Cancer Tissue Cultures Affects Individual Treatment Susceptibility Ex Vivo

“…Therefore, a reduced number of regulating T-cells (Tregs) in the TME and reduced tumor size in immunocompetent mice were shown when combining thiostrepton to oxaliplatin [58]. Although the connection of FOXM1 to the TME is not yet well understood, it is suggested to play a role in T-cell differentiation and to affect the proliferation of macrophages [59,60]. Considering an important influence of immune cells in cancer development and treatment, tissue cultures display a vital immunological compartment [40,61], and thus might help to understand the complex FOXM1 network in context of the TME and the effects of thiostrepton by modulating immune activation.…”