Neutrophils infiltrating pancreatic ductal adenocarcinoma indicate higher malignancy and worse prognosis

Biochem Biophys Res Commun. 2018 Jun 18;501(1):313-319. doi: 10.1016/j.bbrc.2018.05.024. Epub 2018 May 9.

Abstract

CD177 is considered to represent neutrophils. We analyzed mRNA expression level of CD177 and clinical follow-up survey of PDAC to estimate overall survival (OS) from Gene Expression Omnibus (GEO) dataset (GSE21501, containing samples from 102 PDAC patients) by R2 platform (http://r2.amc.nl). We also analyzed correlated genes of CD177 by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to predict the potential relationship between neutrophils and prognosis of PDAC. We then performed hematoxylin and eosin (H&E) staining and immunohistochemical staining of surgical specimens to verify infiltration of neutrophils in PDAC tissues. After analyzing mRNA expression data and clinical follow-up survey provided in the GEO dataset (GSE21501, containing samples from 102 PDAC patients) and clinicopathological data of 23 PDAC patients, we demonstrated that CD177 was correlated with poor prognosis. The univariate Kaplan-Meier survival analysis revealed that OS was inversely associated with increased expression of CD177 (P = 0.012). Expression of phosphodiesterase (PDE)4D was positively related to CD177 in gene correlation analysis (R = 0.413, P < 0.001) by R2 platform. H&E staining and immunohistochemistry of CD177 in 23 PDAC surgical samples showed accumulation of neutrophils in the stroma and blood vessels around the cancer cells. In addition, immunohistochemical staining showed that CD177 was highly expressed in the stroma and blood vessels around tumor tissues of PDAC, which was similar to H&E staining. Expression of CD177 can be used to represent infiltration of neutrophils, which may have potential prognostic value in PDAC.

Keywords: CD177; Inflammation; Neutrophils; Pancreatic ductal adenocarcinoma; Prognosis; RNA-Seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / genetics
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Isoantigens / genetics
  • Isoantigens / metabolism
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Neutrophils / pathology*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • CD177 protein, human
  • GPI-Linked Proteins
  • Isoantigens
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Cell Surface
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4D protein, human