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Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma

Previous studies have shown that pharmacogenomic modeling of circulating tumor and invasive cells (CTICs) can predict response of pancreatic ductal adenocarcinoma (PDAC) to combination chemotherapy, predominantly 5-fluorouracil-based. We hypothesized that a similar approach could be developed to pre...

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Autores principales: Yu, Kenneth H., Ricigliano, Mark, McCarthy, Brian, Chou, Joanne F., Capanu, Marinela, Cooper, Brandon, Bartlett, Andrew, Covington, Christina, Lowery, Maeve A., O’Reilly, Eileen M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315371/
https://www.ncbi.nlm.nih.gov/pubmed/30477242
http://dx.doi.org/10.3390/cancers10120467
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author Yu, Kenneth H.
Ricigliano, Mark
McCarthy, Brian
Chou, Joanne F.
Capanu, Marinela
Cooper, Brandon
Bartlett, Andrew
Covington, Christina
Lowery, Maeve A.
O’Reilly, Eileen M.
author_facet Yu, Kenneth H.
Ricigliano, Mark
McCarthy, Brian
Chou, Joanne F.
Capanu, Marinela
Cooper, Brandon
Bartlett, Andrew
Covington, Christina
Lowery, Maeve A.
O’Reilly, Eileen M.
author_sort Yu, Kenneth H.
collection PubMed
description Previous studies have shown that pharmacogenomic modeling of circulating tumor and invasive cells (CTICs) can predict response of pancreatic ductal adenocarcinoma (PDAC) to combination chemotherapy, predominantly 5-fluorouracil-based. We hypothesized that a similar approach could be developed to predict treatment response to standard frontline gemcitabine with nab-paclitaxel (G/nab-P) chemotherapy. Gene expression profiles for responsiveness to G/nab-P were determined in cell lines and a test set of patient samples. A prospective clinical trial was conducted, enrolling 37 patients with advanced PDAC who received G/nab-P. Peripheral blood was collected prior to treatment, after two months of treatment, and at progression. The CTICs were isolated based on a phenotype of collagen invasion. The RNA was isolated, cDNA synthesized, and qPCR gene expression analyzed. Patients were most closely matched to one of three chemotherapy response templates. Circulating tumor and invasive cells’ SMAD4 expression was measured serially. The CTICs were reliably isolated and profiled from peripheral blood prior to and during chemotherapy treatment. Individual patients could be matched to distinct response templates predicting differential responses to G/nab-P treatment. Progression free survival was significantly correlated to response prediction and ΔSMAD4 was significantly associated with disease progression. These findings support phenotypic profiling and ΔSMAD4 of CTICs as promising clinical tools for choosing effective therapy in advanced PDAC, and for anticipating disease progression.
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spelling pubmed-63153712019-01-09 Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma Yu, Kenneth H. Ricigliano, Mark McCarthy, Brian Chou, Joanne F. Capanu, Marinela Cooper, Brandon Bartlett, Andrew Covington, Christina Lowery, Maeve A. O’Reilly, Eileen M. Cancers (Basel) Article Previous studies have shown that pharmacogenomic modeling of circulating tumor and invasive cells (CTICs) can predict response of pancreatic ductal adenocarcinoma (PDAC) to combination chemotherapy, predominantly 5-fluorouracil-based. We hypothesized that a similar approach could be developed to predict treatment response to standard frontline gemcitabine with nab-paclitaxel (G/nab-P) chemotherapy. Gene expression profiles for responsiveness to G/nab-P were determined in cell lines and a test set of patient samples. A prospective clinical trial was conducted, enrolling 37 patients with advanced PDAC who received G/nab-P. Peripheral blood was collected prior to treatment, after two months of treatment, and at progression. The CTICs were isolated based on a phenotype of collagen invasion. The RNA was isolated, cDNA synthesized, and qPCR gene expression analyzed. Patients were most closely matched to one of three chemotherapy response templates. Circulating tumor and invasive cells’ SMAD4 expression was measured serially. The CTICs were reliably isolated and profiled from peripheral blood prior to and during chemotherapy treatment. Individual patients could be matched to distinct response templates predicting differential responses to G/nab-P treatment. Progression free survival was significantly correlated to response prediction and ΔSMAD4 was significantly associated with disease progression. These findings support phenotypic profiling and ΔSMAD4 of CTICs as promising clinical tools for choosing effective therapy in advanced PDAC, and for anticipating disease progression. MDPI 2018-11-24 /pmc/articles/PMC6315371/ /pubmed/30477242 http://dx.doi.org/10.3390/cancers10120467 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yu, Kenneth H.
Ricigliano, Mark
McCarthy, Brian
Chou, Joanne F.
Capanu, Marinela
Cooper, Brandon
Bartlett, Andrew
Covington, Christina
Lowery, Maeve A.
O’Reilly, Eileen M.
Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma
title Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma
title_full Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma
title_fullStr Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma
title_full_unstemmed Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma
title_short Circulating Tumor and Invasive Cell Gene Expression Profile Predicts Treatment Response and Survival in Pancreatic Adenocarcinoma
title_sort circulating tumor and invasive cell gene expression profile predicts treatment response and survival in pancreatic adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315371/
https://www.ncbi.nlm.nih.gov/pubmed/30477242
http://dx.doi.org/10.3390/cancers10120467
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