Interferon-Induced Protein With Multiple Tetratricopeptide Repeats 3 Is Associated With Response to Chemotherapy and Recurrence but Not With Survival

Pancreas. 2020 Nov/Dec;49(10):1307-1314. doi: 10.1097/MPA.0000000000001691.

Abstract

Objectives: The interferon-induced protein with multiple tetratricopeptide repeats 3 (IFIT3) seems to be associated with the prognosis in pancreatic cancer. Here we clarify whether the heterogeneity of IFIT3 expression affects previous IFIT3 analysis.

Methods: This retrospective study analyzes pancreatic cancer tissue samples retrieved by surgery from 2 independent patient cohorts. Patients underwent either primary surgery (n = 72) or received neoadjuvant chemotherapy (n = 12). Immunohistochemistry assessed IFIT3 expression and its heterogeneity. Complementarily, we analyzed publicly available transcriptomic data (n = 903).

Results: Of the primarily resected tumors, 16.4% were heterogeneous. Patients with IFIT3-negative tumors did not survive longer compared with patients with IFIT3-positive tumors. An analysis of publicly available data confirmed this result. Patients developing lung metastases had the best prognosis (4.8 years) with significantly lower IFIT3 expression compared with liver metastasis (P = 0.0117). Patients receiving neoadjuvant therapy who are IFIT3 negative had a longer disease-free survival (1.2 vs 0.3 years, P = 0.0081).

Conclusions: Low IFIT3 expression is not associated with longer survival. Divergent results from tissue microarray analyses could be explained with tumor heterogeneity. As a single biomarker, IFIT3 is not suitable for predicting disease prognosis. Recurrence of lung metastases and response to neoadjuvant chemotherapy are associated with low IFIT3 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Pancreatic Ductal / chemistry*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / secondary
  • Carcinoma, Pancreatic Ductal / therapy
  • Chemotherapy, Adjuvant
  • Databases, Genetic
  • Disease-Free Survival
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / analysis*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lung Neoplasms / chemistry*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Male
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local
  • Pancreatectomy
  • Pancreatic Neoplasms / chemistry*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Retrospective Studies
  • Time Factors

Substances

  • Biomarkers, Tumor
  • IFIT3 protein, human
  • Intracellular Signaling Peptides and Proteins