Exploratory evaluation of serum circRNA-CDR1as and inflammatory cytokines for brain metastasis status and short-term treatment response in non-small cell lung cancer

<b style="font-family: inherit;">Background:<span style="font-family: inherit;"> This exploratory study evaluated serum circRNA-CDR1as combined with IL-1b, IL-6, and TNF-a in non-small cell lung cancer (NSCLC), with particular attention to brain metastasis status, short-term treatment response, and the reliability of serum biomarker measurement. </span><b style="font-family: inherit;">Methods: <span style="font-family: inherit;"> Archived serum samples from 100 patients were retrospectively analysed, including 65 patients with brain metastasis (BM) and 35 without BM. Serum circRNA-CDR1as was measured by quantitative reverse-transcription PCR (qRT-PCR), whereas IL-1b, IL-6, and TNF-a were measured by enzyme-linked immunosorbent assay (ELISA); conventional serum tumour markers were also assessed. In patients with brain metastasis, paired serum samples were analysed before and after two treatment cycles, and short-term clinical response was evaluated. Receiver operating characteristic (ROC) curves were used to assess the discriminatory value of individual markers and combined models; assay stability and quality-control parameters were evaluated to support the reliability of biomarker measurement. </span><b style="font-family: inherit;">Results: <span style="font-family: inherit;">Patients with BM had higher serum circRNA-CDR1as than those without BM (3.04±0.82 vs 1.92±0.58, P&lt;0.001), with similar increases in IL-1b, IL-6 and TNF-a. The four-marker circRNA-CDR1as/IL-1b/IL-6/TNF-a model showed the strongest discrimination for BM status, with an area under the curve (AUC) of 0.924 (95% CI: 0.875-0.972), sensitivity of 69.2% and specificity of 100.0%. Among patients with BM, circRNA-CDR1as decreased from 3.04±0.82 to 2.45±0.78 after two treatment cycles (P&lt;0.001), alongside reductions in IL-1b, IL-6, and TNF-a. For distinguishing poor short-term response, the combined model achieved an AUC of 0.918 (95% CI: 0.854-0.983), with sensitivity of 91.3% and specificity of 81.0%. </span><b style="font-family: inherit;">Conclusion: <span style="font-family: inherit;">In this exploratory cohort, serum circRNA-CDR1as combined with IL-1b, IL-6, and TNF-a was associated with BM status and poor short-term response; however, the panel cannot replace contrast-enhanced cranial MRI or independently guide treatment decisions, and prospective external validation is required.</span>