Background: Esophageal cancer (EC) remains a leading cause of cancer-related mortality worldwide. Long non-coding RNA IGFL2-AS1 have been implicated in several malignancies, but their roles in EC remain unclear. This study aimed to evaluate the expression and potential regulatory interaction of IGFL2-AS1 and BRCA1 in EC.

Methods: In this study, sixteen paired EC and adjacent non-tumorous tissues were collected. Expression levels of IGFL2-AS1 and BRCA1 were quantified using RT-qPCR, and BRCA1 protein expression was assessed by Western blotting. Bioinformatic analyses were performed using GEPIA, STRING, and g:Profiler to explore expression patterns, survival outcomes, and associated molecular pathways. Statistical analyses included ROC curve evaluation and correlation tests.

Results: Both IGFL2-AS1 and BRCA1 were significantly downregulated in EC tissues compared to adjacent normal controls (p<0.05). A strong positive correlation was observed between their expression levels. ROC analysis indicated significant diagnostic potential for both genes (AUC>0.75), with BRCA1 showing superior accuracy. Western blot confirmed decreased BRCA1 protein levels in tumor samples. In contrast, GEPIA data suggested upregulation of both genes in EC. Functional enrichment linked BRCA1-associated genes to ephrin receptor signaling and axon guidance pathways.

Conclusion: The concurrent downregulation of IGFL2-AS1 gene and BRCA1 at transcript and protein levels suggests a potential regulatory link and highlights their diagnostic relevance in EC. The observed positive correlation between their expression and favorable ROC metrics supports their utility as candidate biomarkers in this disease.