Proteomics-based prognostic signature in colon adenocarcinoma patients with familial adenomatous polyposis.

BACKGROUND

Familial adenomatous polyposis (FAP) is regarded as a precancerous stage of colon adenocarcinoma (COAD). COAD concurrent with FAP is quite rare in colorectal cancer screening. In order to create a new COAD prognostic prediction model and to shed light on the landscape of the tumor immune microenvironment in COAD, we examined differentially expressed genes (DEGs) between COAD and FAP in this study.

METHODS

DEGs between COAD and FAP were identified using proteomic technology. Expression matrix data for COAD were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Using multivariate and least absolute shrinkage and selection operator (LASSO) regression analyses, a prognostic risk model for COAD concurrent with FAP (COAD-FAP) was created. In the training and validation sets, the efficacy of the risk model was confirmed, respectively. A systematic analysis was conducted on the relationships between the prognostic signature and immunological score, tumor immune cell infiltration, and immune checkpoints.

RESULTS

A survival risk model was constructed using four prognostic genes: fatty acid-binding protein 4 (), cysteine-rich protein 2 (), leucine-rich repeat containing helicase 4 (), and tissue inhibitor of metalloproteinases 1 (). The training and testing datasets both provided validation for this model. It was verified by Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curve analysis that the prognosis of COAD could be reliably predicted by these four COAD-FAP risk signatures. The risk score was positively correlated with immune score and immune cell infiltration levels, according to the correlation analysis.

CONCLUSIONS

These findings imply that the four COAD-FAP risk signatures could be a practical tool for forecasting prognostic risk, assessing immunotherapy efficacy, and personalizing customized treatment choices for COAD patients.