Correlation of serum-soluble mesothelin-related protein, HMGB1 and CA125 in diffuse malignant peritoneal mesothelioma and their combined measurement for prognosis

Abstract

Diagnosis of diffuse malignant peritoneal mesothelioma (DMPM) is challenging due to the lack of efficient biomarkers for early-stage DMPM. This study was designed to characterize three serum-soluble mesothelium-related proteins, including soluble mesothelin-related protein (SMRP), high mobility group box 1 (HMGB1), and cancer antigen 125 (CA125) in diagnosing DMPM. Serum samples of DMPM patients and healthy controls were collected and an enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of HMGB1, CA125, and SMRP. Correlations between these three serum proteins were examined and the diagnostic values of the biomarkers were assessed by receiver operating curve (ROC) analysis. The combined expression levels of the three markers were also analyzed in terms of predicting patient survival. Higher levels of CA125, SMRP, and HMGB1 was found to be a prominent characteristic of DMPM patients (with > two-fold higher for all levels in DMPM patients compared to control patients, all p < .001), particularly for those with higher-stage DMPM (stage III-IV) compared with lower-stage DMPM (stage I-II) (all p < .05). HMGB1, CA125, and SMRP were all significantly inter-correlated with each other (all p < .05), the combination of the three serum markers had high sensitivity and specificity for diagnosing DMPM. Combined values of the three markers demonstrated a high AUC of 0.85, sensitivity of 78.95%, specificity of 82.75% for identifying DMPM. The combined level of the three markers also demonstrated a significant positive correlation with poor survival of DMPM patients (p = .022). CA125, SMRP, and HMGB1 are potentially valuable diagnostic biomarkers to facilitate the diagnosis of DMPM.