Computational STAT3 activity inference reveals its roles in the pancreatic tumor microenvironment

Sci Rep. 2019 Dec 3;9(1):18257. doi: 10.1038/s41598-019-54791-x.


Transcription factor (TF) STAT3 contributes to pancreatic cancer progression through its regulatory roles in both tumor cells and the tumor microenvironment (TME). In this study, we performed a systematic analysis of all TFs in patient-derived gene expression datasets and confirmed STAT3 as a critical regulator in the pancreatic TME. Importantly, we developed a novel framework that is based on TF target gene expression to distinguish between environmental- and tumor-specific STAT3 activities in gene expression studies. Using this framework, our results novelly showed that compartment-specific STAT3 activities, but not STAT3 mRNA, have prognostications towards clinical values within pancreatic cancer datasets. In addition, high TME-derived STAT3 activity correlates with an immunosuppressive TME in pancreatic cancer, characterized by CD4 T cell and monocyte infiltration and high copy number variation burden. Where environmental-STAT3 seemed to play a dominant role at primary pancreatic sites, tumor-specific STAT3 seemed dominant at metastatic sites where its high activity persisted. In conclusion, by combining compartment-specific inference with other tumor characteristics, including copy number variation and immune-related gene expression, we demonstrate our method's utility as a tool to generate novel hypotheses about TFs in tumor biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Copy Number Variations
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • STAT3 Transcription Factor / metabolism*
  • STAT3 Transcription Factor / physiology
  • Survival Analysis
  • Tumor Microenvironment*


  • STAT3 Transcription Factor
  • STAT3 protein, human