Circulating sNinj1 as a novel predictor of prognosis and severity in hepatocellular carcinoma

•Serum sNinj1 in HCC patients is significantly higher than in lung cancer, colorectal cancer, systemic lupus erythematosus, rheumatoid arthritis, and normal controls.•Circulating sNinj1 was positively correlated with tumor size, metastasis, and staging in HCC patients.•Serum sNinj1 was significantly high in the HBV-DNA positive subgroup than in the HBV-DNA negative subgroup.•Circulating sNinj1 is another diagnostic biomarker that supports the diagnosis of HCC and reveals potential as a novel predictor of HCC severity and prognosis. The occurrence and development of HCC are closely associated with cell death. Recently, researchers found that Ninj1 plays a pivotal role in PMR during different types of cell death. However, the importance of Ninj1 in HCC has not been extensively investigated. This study included 102 newly diagnosed HCC patients and 102 sex and age-matched NCs. Circulating sNinj1 was assessed by ELISA. Serum LDH and IL-1ß were detected through a chemiluminescence assay. The correlations of these biomarkers with disease severity and their potential as prognostic predictors for HCC were evaluated. The dynamic changes of sNinj1, LDH, and IL-1ß levels before and after treatment were recorded. Serum levels of sNinj1, IL-1ß, and LDH were significantly higher in HCC patients. Our study found that the sNinj1 level was positively correlated with tumor size, metastasis, and staging. ROC analysis indicated that the AUC of sNinj1 in differentiating HCC from NCs was 0.85. As a result of tumor thrombosis and invasion of the hepatic vein, sNinj1′s AUCs were 0.71 and 0.73, respectively. After partial resection and TACE treatment, serum sNinj1 and LDH exhibited similar change trends. A one-year follow-up analysis also demonstrated that HCC patients with high sNinj1 had significantly poorer survival than those with low sNinj1. The serum sNinj1 is another diagnostic biomarker supporting the HCC diagnosis. More importantly, it has been shown that circulating sNinj1 reveals potential as a novel predictor of HCC severity and prognosis.