Changes of serum HMGB1 and IDO levels in patients with esophageal squamous cell carcinoma and their clinical significance
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Abstract:
Objective: To investigate the expression levels of high mobility group protein 1 (HMGB1) and indoleamine-2, 3-dioxygenase (IDO) in serum of patients with esophageal squamous cell carcinoma (ESCC) and their correlation with clinicopathologic features and lymphocyte subsets. Methods: Ninety-five ESCC patients initially hospitalized in the Fourth Hospital of Hebei Medical University from March 2021 to August 2022 were selected as the ESCC group, and the other 40 healthy subjects who underwent physical examination were selected as the control group. The serum levels of HMGB1 and IDO of all subjects and the contents of HMGB1, IDO and p65 in the supernatant of ESCC cell culture in different groups were detected by ELISA. The lymphocyte subsets in the peripheral blood of all subjects were detected by flow cytometry. WB was performed to determine the effect of HMGB1 knockdown as well as HMGB1 knockdown followed by addition of NF-κB signaling pathway activator on the expression levels of HMGB1, IDO and p65 in ESCC cells. Results:The serum levels of HMGB1 and IDO in ESCC group were significantly higher than those in control group (all P<0.01). Elevated serum HMGB1 and IDO levels were the independent risk factors for clinical progression of ESCC (all P<0.01), and their combined detection showed a higher predictive value for the clinical progression of ESCC (P<0.01). Serum HMGB1 and IDO levels were significantly correlated with T stage, N stage and clinical stage in ESCC patients (all P<0.05); Serum HMGB1 levels in ESCC group was negatively correlated with the absolute counts of CD3+ T cells, CD4+ T cells, B cells and NK cells in peripheral blood, and positively correlated with Treg cell percentage (all P<0.05); while serum IDO levels was negatively correlated with percentage and absolute count of CD3+ T cells, CD4+ T cells, and absolute counts of CD8+ T cells and B cells in peripheral blood,but positively correlated with the percentage of Treg cells (all P<0.05). Serum HMGB1 was positively correlated with IDO (P<0.01). The expression levels of IDO and p65 in KYSE30 and ECA109 cells and their culture supernatant in si-HMGB1 group were significantly lower than those in si-NC group and si-HMGB1+PMA group (all P<0.05). Conclusion: Serum HMGB1 and IDO are closely related to the clinical progression of ESCC and immune function of ESCC patients, and have the potential to serve as tumor markers and new immunotherapy targets of ESCC. HMGB1 may promote IDO expression through NF-κB signaling pathway, and dual-target combination therapy may achieve better efficacy.