Transl Oncol. 2025 Dec 1;63:102620. doi: 10.1016/j.tranon.2025.102620. Online ahead of print.
ABSTRACT
BACKGROUND: Gastric cancer (GC) remains a major cause of cancer-related mortality globally, largely due to the absence of reliable non-invasive biomarkers for early detection. Circular RNAs (circRNAs), characterized by covalently closed-loop structures, stability, and detectability in circulation, have emerged as promising liquid biopsy candidates.
METHODS: circAHSA1 (hsa_circ_0032777) was identified through GEO dataset screening (GSE121445) and validated in GC tissues, serum, and cell lines using qRT-PCR with optimized internal reference selection. Diagnostic performance was assessed using ROC analysis and DeLong tests, evaluating circAHSA1 alone and in combination with CEA, CA199, and CA724. Biological functions were examined through proliferation, apoptosis, migration, and invasion assays. Subcellular localization and potential downstream miRNA interactions were analyzed using nuclear-cytoplasmic fractionation and multi-database bioinformatic prediction.
RESULTS: circAHSA1 expression was significantly elevated in GC tissues, serum, and cell lines, and correlated with lymph node metastasis, differentiation status, and TNM stage. Serum circAHSA1 effectively discriminated GC from healthy controls (AUC = 0.787) and gastritis patients (AUC = 0.752), outperforming conventional markers, with statistical superiority confirmed by DeLong analysis. Combined detection further improved diagnostic accuracy (AUC = 0.871). Functionally, silencing circAHSA1 suppressed GC cell proliferation, migration, and invasion while enhancing apoptosis and inducing cell-cycle arrest. Bioinformatic analysis suggested miR-647 and miR-661 as potential downstream targets.
CONCLUSIONS: circAHSA1 is a stable, GC-specific circulating biomarker with both diagnostic and functional relevance. These findings support circAHSA1 as a promising candidate for liquid biopsy-based GC detection and a potential therapeutic target.
PMID:41330006 | DOI:10.1016/j.tranon.2025.102620
