Identification of the SUMOylation Gene Signature in Colon Cancer by Transcriptome and Mendelian Randomization Integration

Background: SUMOylation is a posttranslational protein modification, which is involved in tumorigenesis, aggression, metastasis, drug resistance, and prognosis, while the molecular characteristics and prognostic values of the SUMOylation remain unclear.

Methods: The transcriptomic data were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), and summary-level data of genome-wide association studies (GWAS) and expression quantitative trait locus (eQTL) from European ancestry were collected. The SUMOylation patterns of CRC patients, tumor microenvironment (TME) immune cell infiltrating characteristics, biological function therapeutic responses, and prognostic signatures were identified. Mendelian randomization (MR) analysis explored the causality between prognostic signatures and CRC.

Results: Three SUMOylation-related clusters were classified, and Cluster 2 showed the worst survival status, most populations of infiltrated immune cells, responses to anti-CTLA-4 and anti-PD-1 therapies, and sensitivity to chemotherapy. Nine SUMOylation-related signatures (NDC1, PPARGC1A, CDKN2A, UHRF2, NUP54, PIAS3, H4C4, CHD3, and SUMO2) were selected and validated as prognostic signatures. A predictive nomogram was constructed and validated. Finally, NUP54 was positive, but PPARGC1A was negatively associated with the risk of CRC.

Conclusion: This study first comprehensively explored the molecular characteristics and prognostic values of SUMOylation and identified the possible biomarkers for treatment in CRC.