Double-positive expression of high-mobility group box 1 and vascular endothelial growth factor C indicates a poorer prognosis in gastric cancer patients

Abstract

BackgroundAlthough many studies have indicated that high-mobility group box 1 protein (HMGB1) is associated with oncogenesis and a worse prognosis, the prognostic value of HMGB1 in gastric cancer (GC) remains unclear. In the present work, we aimed to evaluate the role of HMGB1 in GC and examined whether aberrant expression of both HMGB1 and vascular endothelial growth factor C (VEGF-C) increased the malignant potential of GC.MethodsA total of 166 GC patients and 32 normal subjects were enrolled. HMGB1 and VEGF-C expression was detected by tissue microarrays (TMAs) and immunohistochemical staining. The correlation between HMGB1 and VEGF-C expression and their relationships with clinicopathological GC variables were examined. Univariate and multivariate analyses were performed using the Cox proportional hazard model to predict the factors related to the patients‘ overall survival rates.ResultsHMGB1 and VEGF-C expression were observed in 81 (48.80%) and 88 (53.01%) tumors, respectively, significantly higher than the rates among the corresponding controls. In addition, HMGB1 and VEGF-C expression were positively correlated (R2 = 0.972). HMGB1 expression was also closely associated with tumor size, pT stage, nodal status, metastasis status, TNM stage, and poor prognosis. Multivariate survival analysis indicated that patients with HMGB1 and VEGF-C coexpression had the worst prognoses and survival rates (hazard ratio, 2.78; log rank P<0.001).ConclusionsHMGB1 is commonly expressed in GC. Combined evaluation of HMGB1 and VEGF-C may serve as a valuable independent prognostic factor for GC patients.

HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review

“…However, study by Soldevilla et al [19] did not give a well-defined interpretation standard of HMGB1 expression. In addition, the duration of follow-up was not distinctly described in 4 studies of Akaike et al [14], He et al [15], Wittwer et al [24] and Sheng et al [31]. Unfortunately, there was no study mentioning important confounders like the subsequent treatment.…”

Clinical Significance of HMGB1 Expression in Human Gastric Cancer

“…It is shown thatHMGB 1not only contributesto the malignant progression ofhepatocellular carcinoma (23), pancreatic cancer (24) and prostate cancer (25), but also serves as an independent prognostic factor predicting the poor prognosis for these cancers (23)(24)(25). HMGBI expression is observed in gastric cancer, and correlated with metastasis status, TNM stage and poor prognosis, revealing an independent prognostic factor (26). Differently from these studies, individual studies illustrate that overexpression of HMGBI may be a marker of good prognosis of gastric adenocarcinoma patients given curative resection combined with adjuvant chemotherapy (27).…”

Serum HMGB1 is a predictive and prognostic biomarker for oncolytic immunotherapy

“…Several studies suggest that high HMGB1 serum levels [13][14][15] or expression at the tumor site 16,17 correlate with poor prognosis and therapy outcome, while a few studies suggest the opposite. 18,19 In the context of cancer immunotherapy, however, which specifically acts on the immune system where HMGB1 is a key cytokine, the prognostic and predictive value of HMGB1 has not been previously studied.…”

“…12 We and others have shown that immunogenic cell death occurs rapidly after anticancer therapy including oncolytic adenoviruses, 11,22,38,39 rendering it likely that transient local release of HMGB1 is capable of activating dendritic cells and boosting immune response against the tumor. Explaining some of the conflicting findings reported in cancer patients, 15,[17][18][19] this phenomenon may be too spatially and temporally dynamic to be resolved solely by "snapshot" ELISA or immunohistochemistry based assays. In contrast, constitutive secretion of HMGB1 from immune cells at steady state could be an indicator of harmful immunosuppression, 10,34 as trended in our DHMGB1 analyses at late time points (Fig.…”