TM9SF1 as a Novel Prognostic Biomarker for Sepsis Severity and Mortality: A Longitudinal Study

Sepsis is a prevalent and detrimental condition in intensive care units (ICUs) and a leading cause of mortality. The present study evaluated the role and clinical importance of Transmembrane 9 superfamily member 1 (TM9SF1) as a potential indicator for the early detection of sepsis severity and prognosis. This study included 118 patients with septic shock and 107 patients with sepsis, all of whom underwent follow-up assessments. Gene expression of TM9SF1 and cytokines in peripheral blood mononuclear cells (PBMCs) were quantified using qPCR. The predictive role of TM9SF1 was compared with standard clinical markers using receiver operating characteristic (ROC) curve analysis. A nomogram-based predictive model with TM9SF1 was constructed to enable early detection of disease severity and mortality in sepsis patients. TM9SF1 mRNA expression was considerably elevated in the septic shock group relative to the sepsis group and healthy controls (p < 0.001). Increased TM9SF1 levels were associated with higher sepsis severity (OR = 3.29, 95% CI = 1.88-5.78, p < 0.001) and mortality (HR = 11.12, 95% CI = 4.35-28.45, p < 0.001). Moreover, ROC curve analysis showed that TM9SF1 outperformed clinical indicators in predicting sepsis severity and mortality including CRP, oxygenation index and lactate. A nomogram model comprised TM9SF1, CRP, D-dimer, and ESR and predicted sepsis severity (AUC = 0.883, 95% CI = 0.839-0.927), while another model with TM9SF1, CRP, ESR, lactate and oxygenation index predicted patient's mortality (C-index = 0.931; 95% CI = 0.884-0.978). The study concluded that both sepsis severity and mortality were found to increase with higher TM9SF1 levels, suggesting that TM9SF1 has a crucial role in regulating inflammation in sepsis patients by controlling cytokine production. It can serve as a potential novel immune biomarker for the early detection of disease progression and clinical findings in sepsis patients.