An 11-gene signature for the prediction of systemic recurrences in colon adenocarcinoma.

BACKGROUND: Prognosis varies among patients within the same colon adenocarcinoma (COAD) stage, indicating the need for reliable molecular markers to enable individualized treatment. This study aimed to investigate gene signatures that can be used for better prognostic prediction of COAD.

METHODS: Gene-expression profiles of COAD patients were obtained from the Gene Expression Omnibus database ( n  =   332) and The Cancer Genome Atlas database ( n  =   431). The relationship between gene signature and relapse-free survival was analysed in the training set ( n  =   93) and validated in the internal validation set ( n  =   94) and external validation sets ( n  =   145 and 431).

RESULTS: Overall, 11 genes (N-myc downstream regulated gene 1 [ NDRG1 ], fms-like tyrosine kinase 1 [ FLT1 ], lipopolysaccharide binding protein [ LBP ], fatty acid binding protein 4 [ FABP4 ], adiponectin gene [ ADIPOQ ], angiotensinogen gene [ AGT ], activin A receptor, type II-like kinase 1 [ ACVRL1 ], CC chemokine ligand 11 [ CCL11 ], cell division cycle 42 [ CDC42 ], T-cell receptor alpha variable 9_2 [ TRAV9_2 ], and proopiomelanocortin [ POMC ]) were identified by univariable and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Based on the risk-score model, the patients were grouped into the high-risk or low-risk groups using the median risk score as the cut-off. The area under the curve (AUC) values for 1-, 3-, and 5-year recurrence were 0.970, 0.849, and 0.859, respectively. Patients in the high-risk group had significantly poorer relapse-free survival than did those in the low-risk group. The predictive accuracy of the 11-gene signature was proven in the validation sets. Our gene signature showed better predictive performance for 1-, 3-, and 5-year recurrence than did the other four models.

CONCLUSIONS: The 11-gene signature showed good performance in predicting recurrence in COAD. The accuracy of the signature for prognostic classification requires further confirmation.