Ferroptosis-related SOCS1 as a candidate host-response biomarker in tuberculosis: An integrated transcriptomic and...

Suppressor of cytokine signaling 1 (SOCS1) has been implicated in immune regulation and has been identified as a ferroptosis-related candidate gene in tuberculosis (TB) transcriptomic studies. However, its expression characteristics in independent clinical samples and its relationship with disease activity-related indicators remain insufficiently defined. This study integrated public transcriptomic datasets with clinical validation to evaluate SOCS1 expression in TB, assess its potential adjunctive diagnostic value, and explore its clinical associations. Public datasets from the Gene Expression Omnibus were used to identify and validate ferroptosis-related candidate genes associated with TB. SOCS1 expression was evaluated across independent datasets, including whole-blood datasets and an in vitro Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cell model. Peripheral blood SOCS1 mRNA expression was measured by reverse transcription-quantitative polymerase chain reaction in 36 patients with active pulmonary TB and 21 healthy controls. SOCS1 protein expression was assessed by immunohistochemistry in an independent lung tissue cohort. Plasma malondialdehyde and total glutathione levels were measured as oxidative stress-related biochemical indicators using commercial assay kits according to the manufacturers' instructions. Receiver operating characteristic curve and Spearman correlation analyses were used to assess discriminatory performance and clinical associations. SOCS1 was consistently upregulated across independent TB-related datasets and was significantly elevated in peripheral blood from patients with TB compared with healthy controls. In the clinical cohort, SOCS1 showed modest discriminatory performance for distinguishing TB patients from healthy controls, with an area under the curve of 0.731 (95% confidence interval = 0.599-0.864). Immunohistochemistry showed stronger SOCS1 protein expression in TB tissues than in control tissues, whereas pneumonia tissues showed a nonsignificant increasing trend. SOCS1 expression was positively correlated with C-reactive protein, erythrocyte sedimentation rate, and sputum culture grade. Additional biochemical analyses showed higher malondialdehyde and lower total glutathione levels in TB patients, with corresponding correlations with SOCS1 expression. SOCS1 may serve as a ferroptosis-related candidate host-response biomarker with potential adjunctive diagnostic value in TB. Its expression may reflect inflammatory burden, microbiological burden, and oxidative imbalance-related host responses in the context of TB, although further validation and mechanistic studies are required.