Abstract
Leucine-rich α-2 glycoprotein 1 (LRG1) is a secreted glycoprotein implicated in various diseases, yet its role across multiple cancers remains insufficiently explored. Consequently, we conducted a comprehensive bioinformatics analysis, exploring LRG1 expression patterns, prognostic implications, and potential therapeutic associations in a pan-cancer context. Additionally, we collected gene expression and clinical data from patients with kidney renal clear cell carcinoma (KIRC) from TCGA, conducting gene set enrichment analysis (GSEA) and Cox proportional hazards regression analysis to explore the potential regulatory role of LRG1 in KIRC. Our study revealed that LRG1 expression is upregulated in 18 cancer types, with elevated levels correlating with poor prognostic outcomes in several cancers, notably KIRC. Epigenetic analysis showed hypomethylation in the LRG1 promoter region, potentially contributing to the overexpression of LRG1. Moreover, LRG1 expression was linked to immunotherapeutic responses and altered drug sensitivities, particularly influencing the efficacy of tyrosine kinase inhibitors. In KIRC, high LRG1 expression was associated with the activation of key pathways, including angiogenesis, epithelial-mesenchymal transition (EMT), and hypoxia signalling. We identified key gene pairs interacting with LRG1 in KIRC, including CARD14 and CYP8B1, with CARD14 overexpression correlating with poorer clinical outcomes and CYP8B1 indicating a favourable prognosis. In conclusion, LRG1 emerges as a potential biomarker for prognosis and immunotherapy responsiveness in both pan-cancer and KIRC contexts. This study provides a theoretical foundation for further research on the therapeutic potential of target regulating LRG1 in cancer treatment.