RECQL correlates with immune infiltration and serves as a prognostic biomarker and therapeutic predictor in gastric cancer.

Abstract

BACKGROUND: RecQ-like helicase (RECQL), a member of the RecQ-like DNA helicase family, plays a crucial role in maintaining genomic stability. However, its relevance in gastric cancer (GC) has not been fully investigated. This study aimed to explore the clinical significance, biological functions, and potential role of RECQL in the tumor immune microenvironment of GC through comprehensive bioinformatics analyses and in vitro experiments. METHODS: Weighted gene co-expression network analysis (WGCNA), differential expression analysis, and least absolute shrinkage and selection operator (LASSO) regression were performed using public datasets [The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD), GSE150290] to identify key genes associated with GC progression. Subsequently, key pathways were identified through functional enrichment analysis, while immune infiltration and spatial transcriptomic analyses were conducted to characterize RECQL expression and its association with the tumor immune microenvironment. Finally, the effects of RECQL knockdown on the biological function of GC cells were assessed through Cell Counting Kit-8 (CCK-8), colony formation, scratch, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS: RECQL was significantly upregulated in GC tissues and correlated with advanced clinical stage and poor prognosis. Gene set enrichment analysis (GSEA) revealed a strong association between high RECQL expression and DNA repair pathway. Immune infiltration analysis indicated significant enrichment of M2 macrophages in the high-RECQL group, along with upregulation of immune checkpoint molecules including PDCD1, CTLA4, and CD274. Spatial transcriptomics further demonstrated co-localization of RECQL with myeloid cell-enriched regions in tumor parenchymal areas. Furthermore, in vitro experimental results indicated that RECQL was highly expressed in GC cell lines, and its knockdown effectively inhibited the viability, proliferation, and migration capabilities of HGC-27 cells, while enhancing their apoptosis. CONCLUSIONS: RECQL serves as a promising biomarker and potential therapeutic target in GC.