Identification and Validation of the Glycolysis and Immune-related Gene Signature for Prognosis in Colorectal Cancer

Glycolysis has a role in regulating the tumor immune microenvironment. However, the functions and clinical role for facilitating the prognosis prediction of colorectal cancer (CRC) based on glycolysis and immune-related genes remain to be identified.

Genes associated with glycolysis and immunity (GI) were identified from established databases (MSigDB and ImmPort). The TCGA (training cohort) and GSE39582 (validation cohort) datasets were used. Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were applied for model construction. The prognostic power of the GI signature was examined by multivariate Cox regression analysis. The correlations between the GI signature, immune cell infiltration and immune checkpoint blockade (ICB) genes were analyzed. To further validate the identified gene signature, quantitative RT-PCR was performed. Cell proliferation assays were conducted for CCK8 detection.

A new GI model was constructed, and this signature may serve as an independent prognostic biomarker in CRC. The GI signature remained an effective tool for predicting prognosis among each clinical subgroup. This signature was related to immune cell infiltration of myeloid dendritic cells, cancer-associated fibroblasts (CAFs), CD4+ and CD8+ T cells and response to the ICB immunotherapy-related genes IDO1, BTLA, PD-L1 and PD-L2. In addition, our findings showed that PMM2, IL20RB, and NTF4 exhibited high expression levels in CRC. The upregulation of these genes resulted in the promotion of the proliferation of CRC cells.

This novel prognostic signature contributed to CRC risk stratification and survival prediction based on glycolysis and immune status.