Elucidating prognostic significance of purine metabolism in colorectal cancer through integrating data from transcriptomic, immunohistochemical, and single-cell RNA sequencing analysis.

Abstract

Colorectal cancer (CRC) is widely recognized for its high prevalence and significant mortality rates, and purine metabolism has been serving as a potential therapeutic target. However, purine metabolism has not yet been validated as a prognostic marker through immunohistochemical analysis. In this study, we utilized a combination of bulk transcriptome analysis, immunohistochemistry (IHC), and single-cell RNA sequencing (scRNA-seq) to assess the clinical relevance of purine metabolism in CRC. Low expression levels of five purine metabolism-related genes-ADSL, APRT, ADCY3, NME3, and NME6-were associated with worse prognosis in CRC patient subgroups, including wild-type TP53, mutant TP53, and microsatellite-stable phenotypes. IHC-based validation showed that NME3 expression was an independent prognostic factor, whereas ADSL and NME6 expressions were associated with clinical variables in prediction of prognosis. Notably, NME3 expression predicted a high risk in patients with early-stage CRC, while ADSL and NME6 expressions were predictive in late-stage CRC. scRNA-seq analysis showed that four genes, excluding NME6, had low expression levels in epithelial cells at the late-stage CRC. Despite the reversible nature of purine metabolism reactions, we demonstrated a consistent directional expression of these five prognostic purine metabolism-related proteins in CRC tissues. We suggest that alterations in purine metabolism could serve as a clinically useful prognostic marker in CRC.