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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Takatoshi Matsuyama, Toshiaki Ishikawa, Naoki Takahashi, Yasuhide Yamada, Masamichi Yasuno, Tatsuyuki Kawano, Hiroyuki Uetake, Ajay Goel

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. More... »

PAGES

19

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12943-019-0945-y

DOI

http://dx.doi.org/10.1186/s12943-019-0945-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111914732

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30717807


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