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Supplementary Figure S1 from Development and validation of a 15-gene expression signature with superior prognostic ability in stage II colorectal cancer

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posted on 2023-08-07, 14:00 authored by Matjaž Rokavec, Elif Özcan, Jens Neumann, Heiko Hermeking

Supplementary Figure S1 shows pathway analysis and clinico-pathological associations of unfavorable prognostic genes.

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ARTICLE ABSTRACT

Currently, there is no consensus about the use of adjuvant chemotherapy for stage II colorectal cancer (CRC) patients. Here, we aimed to identify and validate a prognostic mRNA expression signature for the stratification of stage II CRC patients according to their risk for relapse. First, publicly available mRNA expression profiling datasets from 792 primary, stage II CRCs from 6 different training cohorts were analyzed to identify genes that are consistently associated with patient relapse free survival (RFS). Second, the identified gene expression signature was experimentally validated using NanoString technology and computationally refined on primary CRC samples from 205 stage II CRC patients. Third, the refined signature was validated in two independent publicly available cohorts of 166 stage II CRC patients. Bioinformatics analysis of training cohorts identified a 61-gene signature that was highly significantly associated with RFS (HR=37.08, p=2.68*10-106, sensitivity=89.29%, specificity=89.61%, and AUC=0.937). The experimental validation and refinement revealed a 15-gene signature that robustly predicted relapse in three independent cohorts: an in-house cohort (HR=20.4, p=8.73*10-23, sensitivity=90.32%, specificity=80.99%, AUC=0.812), GSE161158 (HR=5.81, p=3.57*10-4, sensitivity=64.29%, specificity=81.67%, AUC=0.796), and GSE26906 (HR=7.698, p=7.26*10-8, sensitivity=61.54%, specificity=78.33%, AUC=0.752). In the pooled training cohort the 15-gene signature (HR=4.72, p=7.76*10-25, sensitivity=75%, specificity=67.44%, AUC=0.784) was superior to the Oncotype-DX-colon-7-gene signature (HR=2.698, p=6.3*10-8, sensitivity=62.16%, specificity=55.5%, AUC=0.633). We report the identification and validation of a novel mRNA expression signature for robust prognostication and stratification of stage II CRC patients, with superior performance in the analyzed validation cohorts when compared to clinico-pathologic biomarkers and signatures currently used for stage II CRC prognostication.

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