A glycolysis-related two-gene risk model that can effectively predict the prognosis of patients with rectal cancer

Background: Aerobic glycolysis is an emerging hallmark of cancer. Although some studies have constructed glycolysis-related prognostic models of colon adenocarcinoma (COAD) based on The Cancer Genome Atlas (TCGA) database, whether the COAD glycolysis-related prognostic model is appropriate for distinguishing the prognosis of rectal adenocarcinoma (READ) patients remains unknown. Exploring critical and specific glycolytic genes related to READ prognosis may help us discover new potential therapeutic targets for READ patients.

Results: Three gene sets, HALLMARK_GLYCOLYSIS, REACTOME_GLYCOLYSIS and REACTOME_REGULATION_OF_GLYCOLYSIS_BY_FRUCTOSE_2_6_BISPHOSPHATE_METABOLISM, were both significantly enriched in both COAD and READ through glycolysis-related gene set enrichment analysis (GSEA). We found that six genes (ANKZF1, STC2, SUCLG2P2, P4HA1, GPC1 and PCK1) were independent prognostic genes in COAD, while TSTA3 and PKP2 were independent prognostic genes in READ. Glycolysis-related prognostic model of COAD and READ was, respectively, constructed and assessed in COAD and READ. We found that the glycolysis-related prognostic model of COAD was not appropriate for READ, while glycolysis-related prognostic model of READ was more appropriate for READ than for COAD. PCA and t-SNE analysis confirmed that READ patients in two groups (high and low risk score groups) were distributed in discrete directions based on the glycolysis-related prognostic model of READ. We found that this model was an independent prognostic indicator through multivariate Cox analysis, and it still showed robust effectiveness in different age, gender, M stage, and TNM stage. A nomogram combining the risk model of READ with clinicopathological characteristics was established to provide oncologists with a practical tool to evaluate the rectal cancer outcomes. GO enrichment and KEGG analyses confirmed that differentially expressed genes (DEGs) were enriched in several glycolysis-related molecular functions or pathways based on glycolysis-related prognostic model of READ.

Conclusions: We found that a glycolysis-related prognostic model of COAD was not appropriate for READ, and we established a novel glycolysis-related two-gene risk model to effectively predict the prognosis of rectal cancer patients.