Identification and validation of key genes linked to hyperlipidemia in colorectal adenoma

Colorectal adenoma (CRA) is a major precancerous lesion for colorectal cancer (CRC). This study aimed to identify hyperlipidemia-related genes (HLPRGs) associated with CRA and explore their potential diagnostic value and biological relevance. Transcriptomic data from the GEO database were analyzed to define DEGs between CRA and control samples. Candidate genes were detected through overlapping DEGs with HLPRGs, and core genes were determined using protein-protein interaction analysis and machine learning. Key genes were then chosen based on their expression levels and ROC curve performance. Additionally, GSEA, immune cell infiltration analysis, drug prediction, and molecular docking were performed on key genes. Finally, the expression of key genes was validated in clinical specimens with reverse transcription quantitative polymerase chain reaction (RT-qPCR). A total of 176 candidate genes were detected, followed by the detection of seven core genes. Based on the expression analysis results ( p < 0.05) and diagnostic performance (AUC > 0.9), LCN2, MMP7, and MYC were determined as key genes for CRA. GSEA revealed the key genes were markedly linked to important pathways such as the cell cycle and spliceosome ( p < 0.05). Immune infiltration analysis revealed that resting mast cells and M2 macrophages were significantly negatively correlated with all key genes, while activated mast cells and naive CD4 T cells showed notable positive correlations (|cor| > 0.3, p < 0.05). Furthermore, drug prediction based on key genes yielded 462 candidate drugs. Among them, cyclosporin A exhibited the strongest binding affinities (≤ -11.3 kcal/mol) in molecular docking, suggesting a strong computational interaction. RT-qPCR validation further showed that, compared with the normal control group, the mRNA expression levels of MMP7, MYC, and LCN2 were significantly upregulated in colon tissues from CRA patients. LCN2, MMP7, and MYC may contribute to CRA progression and immune microenvironment remodeling. These findings provide new insights into CRA’s molecular mechanisms and suggest novel therapeutic strategies.