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Significance of STAT3 in Immune Infiltration and Drug Response in Cancer

Wei Chen1, Xiaoshuo Dai1, Yihuan Chen1

  • 1Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.

Biomolecules
|June 4, 2020
PubMed

Insights

Signal transducer and activator of transcription 3 (STAT3) influences cancer immunity and drug response. Lower STAT3 levels correlate with immunosuppression and altered immune cell infiltration, impacting treatment efficacy.

Area of Science:

  • Oncology
  • Immunology
  • Bioinformatics

Background:

  • Signal transducer and activator of transcription 3 (STAT3) is a key transcription factor involved in tumorigenesis.
  • The precise roles of STAT3 in cancer immune infiltration and drug response are not fully understood.

Purpose of the Study:

  • To comprehensively investigate the impact of STAT3 on immune infiltration and drug response in cancer using bioinformatics analyses.
  • To elucidate the relationship between STAT3 expression, immune cell markers, and therapeutic outcomes.

Main Methods:

  • Utilized Tumor Immune Estimation Resource (TIMER), Human Protein Atlas (HPA), and UALCAN databases to analyze STAT3 expression and its relation to tumor stage.
  • Employed TIMER for correlation analysis between STAT3 and immune infiltration markers.
  • Assessed STAT3's association with drug response using the Cancer Cell Line Encyclopedia (CCLE) and Cancer Therapeutics Response Portal (CTRP) databases.

Main Results:

  • STAT3 mRNA levels were generally lower in tumors than normal tissues and showed minimal correlation with tumor stage.
  • Protein expression of STAT3 was reduced in colorectal and renal cancers.
  • STAT3 expression correlated significantly with immune cell infiltration, including tumor-associated macrophages (TAMs), M2 macrophages, T-helper 1 (Th1) cells, regulatory T cells (Tregs), and exhausted T cells.
  • STAT3 demonstrated a strong correlation with responses to specific inhibitors and natural compounds, with notable cell line type dependency.

Conclusions:

  • STAT3 is implicated in regulating immune suppression within the tumor microenvironment.
  • STAT3 status is a significant predictive biomarker for drug response in cancer therapy.
  • Findings offer critical insights into STAT3's dual role in immunosuppression and therapeutic sensitivity, relevant for clinical applications.
Keywords:
STAT3bioinformaticsdrug responseimmune infiltration

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