A clinically feasible multiplex proteomic immunoassay as a novel functional diagnostic for pancreatic ductal adenocarcinoma

Kian Huat Lim, Emma Langley, Feng Gao, Jingqin Luo, Lin Li, Gary Meyer, Phillip Kim, Sharat Singh, Vladamir M. Kushnir, Dayna S. Early, Daniel K. Mullady, Steven A. Edmundowicz, Sachin Wani, Faris M. Murad, Dengfeng Cao, Riad R. Azar, Andrea Wang-Gillam

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

To date, targeted therapy for pancreatic ductal adenocarcinoma (PDAC) remains largely unsuccessful in the clinic. Current genomics-based technologies are unable to reflect the quantitative, dynamic signaling changes in the tumor, and require larger tumor samples that are difficult to obtain in PDAC patients. Therefore, a highly sensitive functional tool that can reliably and comprehensively inform intratumoral signaling events is direly needed to guide treatment decision. We tested the utility of a highly sensitive proteomics-based functional diagnostic platform, Collaborative Enzyme Enhanced Reactive-immunoassay (CEERTM), on fine-needle aspiration (FNA) samples obtained from 102 patients with radiographically-evident pancreatic tumors. Two FNA passes were collected from each patient, hybridized to customized chips coated with an array of capture antibodies, and detected using two enzyme-conjugated antibodies which emit quantifiable signals. We demonstrate that this technique is highly sensitive in detecting total and phosphorylated forms of multiple signaling molecules in FNA specimens, with reasonable correlation of marker intensities between two different FNA passes. Notably, signals of several markers were significantly higher in PDAC compared to non-cancerous samples. In PDAC samples, we found high total c-Met signal to be associated with poor survival, and confirmed this finding using an independent PDAC tissue microarray.

Original languageEnglish
Pages (from-to)24250-24261
Number of pages12
JournalOncotarget
Volume8
Issue number15
DOIs
StatePublished - Jan 1 2017

Keywords

  • Fine-needle aspiration
  • Pancreatic cancer
  • Prognosis
  • Proteomics
  • Signaling events

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