TM9SF1 offers utility as an efficient predictor of clinical severity and mortality among acute respiratory distress syndrome patients

Introduction: Acute respiratory distress syndrome (ARDS) is a major cause of death among critically ill patients in intensive care settings, underscoring the need to identify biomarkers capable of predicting ARDS patient clinical status and prognosis at an early time point. This study specifically sought to explore the utility and clinical relevance of TM9SF1 as a biomarker for the early prediction of disease severity and prognostic outcomes in patients with ARDS.

Methods: This study enrolled 123 patients with severe ARDS and 116 patients with non-severe ARDS for whom follow-up information was available. The mRNA levels of TM9SF1 and cytokines in peripheral blood mononuclear cells from these patients were evaluated by qPCR. The predictive performance of TM9SF1 and other clinical indicators was evaluated using received operating characteristic (ROC) curves. A predictive nomogram was developed based on TM9SF1 expression and evaluated for its ability in the early prediction of severe disease and mortality in patients with ARDS.

Results: TM9SF1 mRNA expression was found to be significantly increased in patients with severe ARDS relative to those with non-severe disease or healthy controls. ARDS severity increased in correspondence with the level of TM9SF1 expression (odds ratio [OR] = 2.43, 95% confidence interval [CI] = 2.15-3.72, P = 0.005), and high TM9SF1 levels were associated with a greater risk of mortality (hazard ratio [HR] = 2.27, 95% CI = 2.20-4.39, P = 0.001). ROC curves demonstrated that relative to other clinical indicators, TM9SF1 offered superior performance in the prediction of ARDS severity and mortality. A novel nomogram incorporating TM9SF1 expression together with age, D-dimer levels, and C-reactive protein (CRP) levels was developed and was used to predict ARDS severity (AUC = 0.887, 95% CI = 0.715-0.943). A separate model incorporating TM9SF1 expression, age, neutrophil-lymphocyte ratio (NLR), and D-dimer levels (C-index = 0.890, 95% CI = 0.627-0.957) was also developed for predicting mortality.

Conclusion: Increases in ARDS severity and patient mortality were observed with rising levels of TM9SF1 expression. TM9SF1 may thus offer utility as a novel biomarker for the early prediction of ARDS patient disease status and clinical outcomes.