Survival of patients with gastrointestinal cancers can be predicted by a surrogate microRNA signature for cancer stem-like cells marked by dclk1 kinase

Nathaniel Weygant, Yang Ge, Dongfeng Qu, John S. Kaddis, William L. Berry, Randal May, Parthasarathy Chandrakesan, Edwin Bannerman-Menson, Kenneth J Vega, James J. Tomasek, Michael S. Bronze, Guangyu An, Courtney W. Houchen

Research output: Contribution to journalArticle

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Abstract

Doublecortin-like kinase 1 (DCLK1) is a gastrointestinal (GI) tuft cell kinase that has been investigated as a biomarker of cancer stem-like cells in colon and pancreatic cancers. However, its utility as a biomarker may be limited in principle by signal instability and dilution in heterogeneous tumors, where the proliferation of diverse tumor cell lineages obscures the direct measurement of DCLK1 activity. To address this issue, we explored the definition of a miRNA signature as a surrogate biomarker for DCLK1 in cancer stem-like cells. Utilizing RNA/ miRNA-sequencing datasets from the Cancer Genome Atlas, we identified a surrogate 15-miRNA expression signature for DCLK1 activity across several GI cancers, including colon, pancreatic, and stomach cancers. Notably, Cox regression and Kaplan-Meier analysis demonstrated that this signature could predict the survival of patients with these cancers. Moreover, we identified patient subgroups that predicted the clinical utility of this DCLK1 surrogate biomarker. Our findings greatly strengthen the clinical significance for DCLK1 expression across GI cancers. Further, they provide an initial guidepost toward the development of improved prognostic biomarkers or companion biomarkers for DCLK1-targeted therapies to eradicate cancer stem-like cells in these malignancies.

Original languageEnglish (US)
Pages (from-to)4090-4099
Number of pages10
JournalCancer Research
Volume76
Issue number14
DOIs
StatePublished - Jul 15 2016

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Gastrointestinal Neoplasms
Neoplastic Stem Cells
MicroRNAs
Phosphotransferases
Survival
Biomarkers
Colonic Neoplasms
Neoplasms
Pancreatic Neoplasms
RNA Sequence Analysis
Atlases
Kaplan-Meier Estimate
Cell Lineage
Stomach Neoplasms
Genome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Survival of patients with gastrointestinal cancers can be predicted by a surrogate microRNA signature for cancer stem-like cells marked by dclk1 kinase. / Weygant, Nathaniel; Ge, Yang; Qu, Dongfeng; Kaddis, John S.; Berry, William L.; May, Randal; Chandrakesan, Parthasarathy; Bannerman-Menson, Edwin; Vega, Kenneth J; Tomasek, James J.; Bronze, Michael S.; An, Guangyu; Houchen, Courtney W.

In: Cancer Research, Vol. 76, No. 14, 15.07.2016, p. 4090-4099.

Research output: Contribution to journalArticle

Weygant, N, Ge, Y, Qu, D, Kaddis, JS, Berry, WL, May, R, Chandrakesan, P, Bannerman-Menson, E, Vega, KJ, Tomasek, JJ, Bronze, MS, An, G & Houchen, CW 2016, 'Survival of patients with gastrointestinal cancers can be predicted by a surrogate microRNA signature for cancer stem-like cells marked by dclk1 kinase', Cancer Research, vol. 76, no. 14, pp. 4090-4099. https://doi.org/10.1158/0008-5472.CAN-16-0029
Weygant, Nathaniel ; Ge, Yang ; Qu, Dongfeng ; Kaddis, John S. ; Berry, William L. ; May, Randal ; Chandrakesan, Parthasarathy ; Bannerman-Menson, Edwin ; Vega, Kenneth J ; Tomasek, James J. ; Bronze, Michael S. ; An, Guangyu ; Houchen, Courtney W. / Survival of patients with gastrointestinal cancers can be predicted by a surrogate microRNA signature for cancer stem-like cells marked by dclk1 kinase. In: Cancer Research. 2016 ; Vol. 76, No. 14. pp. 4090-4099.
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