Circulating tumor and invasive cell gene expression profile predicts treatment response and survival in pancreatic adenocarcinoma Journal Article


Authors: Yu, K. H.; Ricigliano, M.; McCarthy, B.; Chou, J. F.; Capanu, M.; Cooper, B.; Bartlett, A.; Covington, C.; Lowery, M. A.; O’Reilly, E. M.
Article Title: Circulating tumor and invasive cell gene expression profile predicts treatment response and survival in pancreatic adenocarcinoma
Abstract: 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 ∆SMAD4 was significantly associated with disease progression. These findings support phenotypic profiling and ∆SMAD4 of CTICs as promising clinical tools for choosing effective therapy in advanced PDAC, and for anticipating disease progression. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords: gemcitabine; pancreatic cancer; 5-fluorouracil; nab-paclitaxel; smad4; folfirinox; circulating tumor and invasive cells
Journal Title: Cancers
Volume: 10
Issue: 12
ISSN: 2072-6694
Publisher: MDPI  
Date Published: 2018-12-01
Start Page: 467
Language: English
DOI: 10.3390/cancers10120467
PROVIDER: scopus c7 - 467
PUBMED: 30477242
PMCID: PMC6315371
DOI/URL:
Notes: Export Date: 2 January 2019 -- Article -- Source: Scopus
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MSK Authors
  1. Joanne Fu-Lou Chou
    157 Chou
  2. Marinela Capanu
    211 Capanu
  3. Maeve Aine Lowery
    98 Lowery
  4. Kenneth Ho-Ming Yu
    65 Yu
  5. Eileen O'Reilly
    324 O'Reilly