MZB1 in borderline resectable pancreatic cancer resected after neoadjuvant chemoradiotherapy

J Surg Res. 2017 Dec:220:391-401. doi: 10.1016/j.jss.2017.07.003. Epub 2017 Sep 3.

Abstract

Background: A high accumulation of CD8+ tumor-infiltrating lymphocytes (TILs) induced by neoadjuvant chemoradiotherapy (NACRT) is associated with a favorable prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). However, the correlation between a high accumulation of CD8+ TILs and a favorable prognosis has yet to be fully clarified. The aim of this study was to determine predictive markers of a high accumulation of CD8+ TILs, with a favorable prognosis, using proteomic analysis.

Materials and methods: We studied 72 resected borderline resectable PDAC patients treated with NACRT between April 2009 and March 2014. Three matched pairs of high CD8+ TIL patients with a favorable prognosis and low CD8+ TIL patients with a poor prognosis were selected. Shotgun proteomics of the stroma and cancerous lesion was performed using formalin-fixed, paraffin-embedded tissue. Validation of the identified proteins was performed using immunohistochemical staining. Relationships between the identified proteins and TILs and clinical outcomes were assessed.

Results: Marginal zone B- and B1-cell-specific protein (MZB1) was detected in the tumor stroma. MZB1 expression was positively correlated with a high accumulation of CD8+ TILs. High stromal MZB1 expression also correlated with disease-free and overall survival. In a subgroup analysis of CD8+ expression, there was a significant association between stromal MZB1 expression and disease-free and overall survival in the high CD8+ TIL group.

Conclusions: MZB1 is a potential marker of a high accumulation of CD8+ TILs in borderline resectable PDACs resected after NACRT. Combination of CD8+ TILs with MZB1 may be a new biomarker of resected cases after NACRT.

Keywords: MZB1; Neoadjuvant chemoradiotherapy; Pancreatic ductal adenocarcinoma; Proteomic analysis; Tumor immunity.

Publication types

  • Validation Study

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Aged
  • Biomarkers / metabolism
  • CD8-Positive T-Lymphocytes*
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / therapy
  • Chemoradiotherapy, Adjuvant
  • Cytokines / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / therapy
  • Proteomics

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Cytokines
  • MZB1 protein, human