Transcriptomic expression profiling identifies ITGBL1, an epithelial to mesenchymal transition (EMT)-associated gene, is a promising recurrence prediction biomarker in colorectal cancer.

ABSTRACT: The current histopathological risk-stratification criteria in colorectal cancer (CRC) patients following a curative surgery remain inadequate. In this study, we undertook a systematic, genomewide, biomarker discovery approach to identify and validate key EMT-associated genes that may facilitate recurrence prediction in CRC. Genomewide RNA expression profiling results from two datasets (GSE17538; N =?173 and GSE41258; N =?307) were used for biomarker discovery. These results were independently validated in two, large, clinical cohorts (testing cohort; N =?201 and validation cohort; N =?468). We performed Gene Set Enrichment Analysis (GSEA) for understanding the function of the candidate markers, and evaluated their correlation with the mesenchymal CMS4 subtype. We identified integrin subunit beta like 1 (ITGBL1) as a promising candidate biomarker, and its high expression associated with poor overall survival (OS) in stage I-IV patients and relapse-free survival (RFS) in stage I-III patients. Subgroup validation in multiple independent patient cohorts confirmed these findings, and demonstrated that high ITGBL1 expression correlated with shorter RFS in stage II patients. We developed a RFS prediction model which robustly predicted RFS (the area under the receiver operating curve (AUROC): 0.74; hazard ratio (HR): 2.72) in CRC patients. ITGBL1 is a promising EMT-associated biomarker for recurrence prediction in CRC patients, which may contribute to improved risk-stratification in CRC.

SUBMITTER: Matsuyama T 

PROVIDER: S-EPMC6360655 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature