A novel model based on protein post-translational modifications comprising the immune landscape and prediction of colorectal cancer prognosis

Background: Phosphorylation is a critical post-translational modification (PTM) type contributing to colorectal cancer (CRC). The study aimed to construct a nomogram model to predict colon adenocarcinoma (COAD) prognosis based on PTM signatures.

Methods: The Cancer Genome Atlas (TCGA) database has been indexed for COAD patients' RNA sequencing, proteomic data, and clinical details. To find potential PTM prognostic signatures, the least absolute shrinkage and selection operator (LASSO) was deployed. Model validation procedures included the use of the Kaplan-Meier (K-M) method, the receiver operating characteristic (ROC) curve, the area under the curve (AUC), and the decision curve analysis (DCA). Additionally, biological enrichment, tumor immune microenvironment, and chemotherapy were also assessed. To validate the model, CRC cells were used in in vitro experiments using western blotting, proliferation assay, colony formation assay, and flow cytometry.

Results: The LASSO regression analysis identified 8 PTM sites. Based on the median PTM score, patients were classified into low- and high-risk groups. K-M results showed that high-risk patients had worse prognoses (P<0.001). Our model demonstrated powerful effectiveness and predictive value (TCGA whole group: 1-year AUC =0.611, 2-year AUC =0.574, 3-year AUC =0.627). Additionally, high-risk CRC patients were enriched in KRAS signaling pathways (P=0.01), possessed more robust immune escape capacity (P=0.001, and induced cell-cycle arrest of CRC cells (P<0.01).

Conclusions: We established and validated a novel nomogram model related to PTM that can predict prognosis and guide the treatment of COAD.