Serum circFUT8 in gastric cancer: Diagnostic performance and clinicopathological associations

Gastric cancer (GC) remains a major cause of cancer-related morbidity and mortality, and biomarkers that complement current diagnostic approaches are needed. Circular RNAs (circRNAs) are promising biomarker candidates because of their stability. We characterized circFUT8 and evaluated its potential as an auxiliary serum biomarker for GC. Its circular structure and stability were assessed by back-splice junction validation, freeze-thaw and room-temperature stability assays, actinomycin D treatment, and ribonuclease R (RNase R) digestion. Real-time quantitative PCR (RT-qPCR) was used to measure circFUT8 expression in 45 pairs of GC and adjacent non-tumor tissues and in serum from 102 patients with GC, 32 patients with gastritis, and 78 healthy controls. CircFUT8 was generated by back-splicing of exons 3–6 of FUT8 and showed a distinct back-splice junction, stability under the tested conditions, and resistance to RNase R digestion. CircFUT8 expression was increased in GC tissues and serum. Serum circFUT8 distinguished GC from healthy controls, gastritis, and pooled non-GC controls, with areas under the receiver operating characteristic curve (AUCs) of 0.725, 0.756, and 0.734, respectively. Combining circFUT8 with carcinoembryonic antigen (CEA) and CA19-9 yielded the highest apparent AUC of 0.765 against healthy controls (optimism-corrected AUC, 0.756). However, the combined models did not significantly outperform circFUT8 alone. Higher serum circFUT8 levels, analyzed as a continuous variable, were associated with poorly differentiated or undifferentiated histology, lymph node metastasis, higher T stages, and advanced tumor-node-metastasis (TNM) stages. CircFUT8 also showed modest discriminatory performance for T1 and TNM stage I–II disease in exploratory analyses. These findings support serum circFUT8 as a candidate auxiliary biomarker for GC, pending validation in larger, independent cohorts.