Exosomal 3’tiRNA-PheGAA and interleukin-6 as novel biomarkers for non-invasive detection of NSCLC

BACKGROUND: Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related mortality worldwide. However, the diagnostic sensitivity and specificity of commonly used tumor markers, such as carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA21-1), remain limited. This study aimed to evaluate the diagnostic value of serum exosomal 3'tiRNA-PheGAA and interleukin-6 (IL-6), alone and in combination with conventional tumor markers, for the detection of NSCLC. METHODS: Peripheral blood samples were collected from 110 patients with NSCLC and healthy controls. Serum exosomes were isolated, and the expression of 3'tiRNA-PheGAA was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Serum levels of CEA, CYFRA21-1, and IL-6 were determined by electrochemiluminescence immunoassay (ECLIA). The diagnostic performance of individual and combined biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Serum levels of 3'tiRNA-PheGAA, IL-6, CEA, and CYFRA21-1 were significantly higher in NSCLC patients than in healthy controls (P < 0.0001). ROC analysis showed that the area under the curve (AUC) values for 3'tiRNA-PheGAA and IL-6 were 0.680 and 0.898, respectively. The combination of 3'tiRNA-PheGAA and IL-6 increased the AUC to 0.926, while the four-marker panel (3'tiRNA-PheGAA, IL-6, CEA, and CYFRA21-1) achieved the highest diagnostic performance with an AUC of 0.971. CONCLUSIONS: Serum exosomal 3'tiRNA-PheGAA and IL-6 may serve as promising non-invasive biomarkers for NSCLC diagnosis, and their combination with conventional tumor markers significantly improves diagnostic accuracy.