A Gene Expression Signature Of 37 Genes Improves Survival Prognosis In Colon Cancer Patients.

Abstract Colon cancer is one of the most prevalent and most deadly types of cancer. Identification of the patients with worse prognosis could improve the results of the therapeutic strategies. In order to achieve this, we present a 37 gene expression signature which improves the state-of-the-art signatures prediction.RNASeq data from the TCGA-COAD cohort have been used to create the model. In this case, a multivariate filtering based on correlation indexes approach was used for feature selection. The finally selected features present a high correlation with the dependent variable but a low correlation among them. These features, together with specific clinical covariates (stage, gender, MSI status, molecular subtype and age at diagnosis) have been used as dependent features in a Cox Proportional Hazard model (CPH). Subsequently, an internal and an external validation of the model were carried out. For the external validation, five independent external cohorts were used. In addition, our signature was compared with four top characterised signatures in colon cancer.In the internal validation, our signature shows higher accuracy than random gene sets, as well as with different known signatures including commercial gene expression based signatures. External validation shows how our signature achieves the best performance. The results obtained in the external validation are shown in Table 1. Comparative analysis of colon risk signatures in external cohorts.CohortPerformance37-geneMDA114ColoGuideExColoGuideProColoPrintTCGA (test)AUC0,630,560,590,590,63n=33HR1,34 (1,02-1,77)1,14 (0,97-1,35)2,13 (1,03-4,40)2,37 (0,94-5,96)2,12 (0,96-4,68)C-Index0,72 (0,52-0,93)0,70 (0,50-0,90)0,65 (0,44-0,85)0,64 (0,43-0,84)0,67 (0,46-0,87)GSE17536AUC0,700,750,680,750,62n=177HR1,47 (1,30-1,67)1,14 (1,08-1,20)1,97 (1,56-2,48)2,86 (2,12-3,86)1,74 (1,37-2,22)C-Index0,70 (0,63-0,77)0,66 (0,59-0,73)0,70 (0,63-0,78)0,74 (0,67-0,81)0,67 (0,60-0,74)GSE17537AUC0,780,560,770,760,68n=55HR1,68 (1,31-2,14)1,05 (0,95-1,17)2,69 (1,67-4,31)2,47 (1,58-3,88)2,00 (1,24-3,22)C-Index0,76(0,63-0,89)0,57 (0,44-0,70)0,75 (0,62-0,88)0,75 (0,62-0,88)0,68 (0,55-0,81)GSE29621AUC0,750,600,690,750,72n=65HR3,47 (1,93-6,24)1,09 (0,97-1,22)2,32 (1,43-3,78)3,43 (1,88-6,23)2,05 (1,28-3,29)C-Index0,77 (0,65-0,89)0,58 (0,46-0,70)0,69 (0,57-0,81)0,76 (0,63-0,88)0,72 (0,60-0,85)GSE39582AUC0,720,640,700,730,63n=185HR1,38 (1,20-1,58)1,09 (1,03-1,16)2,84 (1,99-4,04)2,23 (1,65-3,03)1,36 (1,09-1,71)C-Index0,68 (0,60-0,76)0,61 (0,53-0,69)0,68 (0,60-0,77)0,68 (0,60-0,76)0,60 (0,51-0,68)SummaryAUC0,720,620,690,710,66HR1,87 (1,35-2,68)1,1 (1,00-1,22)2,39 (1,54-3,80)2,67 (1,63-4,59)1,86 (1,19-3,02)C-Index0,73 (0,61-0,85)0,62 (0,50-0,75)0,70 (0,57-0,82)0,71 (0,59-0,83)0,67 (0,54-0,79) Citation Format: Jose Liñares-Blanco, Carlos Fernandez-Lozano, Jose A. Seoane. A gene expression signature of 37 genes improves survival prognosis in colon cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 763.