High-mobility group protein 1 (HMGB1) is an independent predictor of poor survival in ovarian cancer

HMGB1 is a nuclear factor and a secreted damage associated molecular pattern (DAMP) that has a range of functions depending on its subcellular and extracellular localisation, redox state, and interaction with other cell surface receptors. HMGB1 has been implicated in numerous tumour types where expression levels may regulate tumour cell growth and survival as well as altering inflammatory cell recruitment to the tumour.
Using tissue microarrays of primary ovarian cancers and compiling a comprehensive database of clinicopathological variables, the expression of HMGB1 was assessed by immunohistochemistry in test (n=360) and validation (n=194) cohorts. This data was used to correlate HMGB1 expression with patient survival.
In the test cohort 360 ovarian tumours were stained for HMGB1. 10% could not be evaluated due to the absence of enough tissue core or no evaluable tumour cells (i.e. all stroma) in the core. Of the 316 evaluable Ovarian tumours stained with a HMGB1 specific antibody, only 23/360 (7%) tumours failed to stain. A further 42/316 (13%) stained weakly, 52/329 (87%) stained strongly. Kaplan-Meier analysis showed there was a correlation of HMGB1 expression and survival with low expression of HMGB1 being protective (p=0.002). This was replicated in the second cohort (overall survival p=0.077, progression free survival p=0.023). After multivariate analysis HMGB1 remained an independent prognostic factor (p=0.02). In a multivariate model TNM stage (p=<0.0001), tumour type (p=<0.031), response to chemotherapy (p=<0.0001), and HMGB1 expression (p=0.002) were independent predictors of patient survival.
HMGB1 is an independent predictor of poor survival in ovarian cancer. This suggests HMGB1 may be a valuable biomarker and therapeutic target.