Abstract
We investigated the significance of high- mobility group box1 (HMGB1) and T-cell-mediated immunity and prognostic value in cervical cancer. HMGB1, forkhead/winged helix transcription factor p3 (Foxp3), IL-2, and IL-10 protein expression was analyzed in 100 cervical tissue samples including cervical cancer, cervical intraepithelial neoplasia (CIN), and healthy control samples using immunohistochemistry. Serum squamous cell carcinoma antigen (SCC-Ag) was immunoradiometrically measured in 32 serum samples from 37 cases of squamous cervical cancer. HMGB1 and SCC-Ag were then correlated to clinicopathological characteristics. HMGB1 expression tends to increase as cervical cancer progresses and it was found to be significantly correlated to FIGO stage and lymph node metastasis. These findings suggest that HMGB1 may be a useful prognostic indicator of cervical carcinoma. In addition, there were significant positive relationships between HMGB1 and FOXP3 or IL-10 expression (both p < 0.05). In contrast, HMGB1 and IL-2 expression was negatively correlated (p < 0.05). HMGB1 expression may activate Tregs or facilitate Th2 polarization to promote immune evasion of cervical cancer. Elevated HMGB1 protein in cervical carcinoma samples was associated with a high recurrence of HPV infection in univariate analysis (p < 0.05). HMGB1 expression and levels of SCC-Ag were directly correlated in SCC (p < 0.05). Thus, HMGB1 may be a useful biomarker for patient prognosis and cervical cancer prediction and treatment.
Highlights
The human immune system has a close relationship with tumor occurrence and development
These results indicate that High-mobility group box 1 protein (HMGB1) is overexpressed in cervical carcinoma cells and may increase as cervical cancer progresses
These findings suggest that HMGB1 may be a useful prognostic and diagnostic indicator of cervical carcinoma
Summary
The human immune system has a close relationship with tumor occurrence and development. The relative number of Langer’s cells was shown to decrease significantly in local cervical tissue as the level of Foxp protein expression increased This preliminarily confirmed that Tregs are associated with local cervical immune regulation [12]. Whether Treg cells can be activated by HMGB1 in cervical cancer is unclear, and how HMGB1 can influence effector T cells needs further research This merits speculation that through binding to the RAGE receptor, HMGB1 may help cervical cells evade immunosuppression, and accelerate the process of “HPV infection to CIN to cervical cancer” by influencing T cell-mediated immunity. Some studies have shown that high levels of expression of serum SCC-Ag may be associated with advanced disease stages, involvement of lymph nodes, tumor size, and poor response to treatment [16]. All relationships with clinicopathological parameters were analyzed
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