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Published on: July 20, 2019
Widespread parainflammation in human cancer
Dvir Aran1, Audrey Lasry2, Adar Zinger2
1Institute for Computational Health Sciences, University of California, San Francisco, California, 94158, USA.
Parainflammation, a low-grade inflammatory state, is common in human cancers, especially those with p53 mutations. This finding suggests parainflammation may drive cancer and that NSAIDs could offer protection.
Area of Science:
- Oncology
- Inflammation Biology
- Molecular Biology
Background:
- Chronic inflammation is a known hallmark of cancer.
- Parainflammation, a distinct inflammatory state, was previously shown to promote mouse gut tumorigenesis after p53 loss.
- This study investigates parainflammation in human cancers.
Purpose of the Study:
- To determine the prevalence of parainflammation in human cancers.
- To explore the relationship between parainflammation and molecular/clinical parameters.
- To assess the potential role of parainflammation in cancer development and treatment.
Main Methods:
- Development of a transcriptome signature to identify parainflammation.
- Analysis of primary human tumors and carcinoma cell lines.
- Comparison with normal tissues and tumor microenvironments.
Main Results:
- Parainflammation was identified in numerous human tumors and cell lines.
- Parainflammation-positive tumors showed enrichment for p53 mutations.
- These tumors were associated with a poorer prognosis.
- Non-steroidal anti-inflammatory drug (NSAID) treatment reduced parainflammation in murine and human cancers.
Conclusions:
- Parainflammation is widely prevalent in human cancers, particularly those with p53 mutations.
- Parainflammation may drive p53 mutagenesis.
- NSAID treatment may offer a strategy for cancer prevention.
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