Clinical relevance of EMT and stem-like gene expression in circulating tumor cells of metastatic colorectal cancer patients View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-01

AUTHORS

Y Ning, W Zhang, D L Hanna, D Yang, S Okazaki, M D Berger, Y Miyamoto, M Suenaga, M Schirripa, A El-Khoueiry, H-J Lenz

ABSTRACT

Using approved methods, circulating tumor cells (CTCs) are only isolated from blood in 30%-50% of metastatic colorectal cancer (mCRC) patients. We previously validated a technique to isolate circulating tumor cells (CTCs) in a cohort of mCRC patients by combining immunomagnetic enrichment of EpCAM+/CD45- cells with qRT-PCR amplification of CK20 and survivin expression. Here, we examined the prognostic utility of CTC epithelial-mesenchymal transition (EMT) and stem cell gene expression. An 8 ml blood sample was collected from 78 consecutive mCRC patients before treatment with investigational and standard chemotherapeutics. The mRNA expression of EMT (PI3Kα, Akt-2, Twist1) and stem cell (ALDH1) markers was measured. Associations between CTC gene expression and progression-free survival (PFS) and overall survival (OS) were determined using Cox regression models. Among patients without CK20 or survivin-expressing CTCs (n=17), 55% had expression of ALDH1, PI3Kα and/or Akt-2. Patients with positive CTC Akt-2 expression had a significantly shorter median PFS (3.0 versus 4.0 months) compared with those without CTC Akt-2 expression in univariable (hazard ratio (HR)=1.61; log-rank P=0.034) and multivariable analyses (HR=1.70; adjusted P=0.041). In univariable analysis, CTC ALDH1 expression was associated with shorter OS (10.0 versus 38.6 months; HR=2.04, P=0.021). Patients with CTCs expressing ALDH1, PI3Kα and/or Akt-2 had a significantly inferior PFS (3.0 versus 7.7 months; HR=1.88, P=0.015) and OS (10.0 versus 26.8+ months; HR=2.25, P=0.050) in univariable, but not multivariable, analysis. CONCLUSIONS: CTC Akt-2 expression may serve as a clinically useful prognostic marker in mCRC patients and warrants further evaluation in prospective trials. More... »

PAGES

29

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/tpj.2016.62

DOI

http://dx.doi.org/10.1038/tpj.2016.62

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012998388

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27503579


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