CREC Family Genes as Biomarkers and Therapeutic Targets in Lung Adenocarcinoma: In vitro and In silico Insights

Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC), characterized by poor prognosis and limited treatment options.

This study investigated the expression patterns and functional roles of the CREC family genes (RCN1, RCN2, RCN3, SDF2, and CALU) in LUAD using vari-ous detailed molecular and in silico experiments.

RT-qPCR analysis revealed significant upregulation of all five genes in LUAD cell lines compared to normal controls, with ROC curve analysis suggesting their potential as di-agnostic biomarkers. Validation using independent datasets (Oncomine, UALCAN, and HPA) confirmed these findings at both the transcript and protein levels. Stage-specific ex-pression and promoter methylation analyses demonstrated that RCN1 and CALU exhibit higher expression in advanced stages, while promoter hypomethylation correlated with gene overexpression in LUAD. Mutation and copy number variation (CNV) analyses indicated that CREC gene alterations are common in LUAD, with CALU and RCN3 frequently mu-tated. Functional assays revealed that knockdown of SDF2 and CALU significantly reduced cell proliferation, colony formation, and wound healing abilities in A549 cells, suggesting their roles in promoting LUAD progression. Gene enrichment and miRNA interaction anal-yses highlighted the involvement of CREC genes in processes like calcium binding, oxida-tive stress response, and immune regulation. CALU emerged as a potential prognostic mark-er, showing a significant association with poorer survival outcomes.

Together, the findings of this study suggested that CREC family genes may serve as promising diagnostic and therapeutic targets in LUAD.