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Dysregulation in nucleic acid-sensing pathway genes is associated with cancer patients' prognosis

Huo Yan-Fei1, Yang Han1, Zhou Yan-Ting1

  • 1Department of Pathology, School of Basic Medical Sciences, Third Hospital, Peking University Health Science Center, Beijing, China.

Cancer Science
|May 12, 2020
PubMed

Insights

The innate immune system recognizes nucleic acids from microbes and damaged cancer cells. Upregulated nucleic acid-sensing pathways are linked to poorer cancer prognosis, but offer therapeutic potential in specific patient groups.

Area of Science:

  • Immunology
  • Oncology
  • Genomics

Background:

  • The innate immune system uses nucleic acid-sensing receptors to detect microbial invaders.
  • These receptors also recognize nucleic acids released by damaged cancer cells, linking innate immunity to cancer.
  • Targeting nucleic acid-sensing pathways offers potential for novel antitumor therapies.

Purpose of the Study:

  • To systematically analyze the dysregulation of nucleic acid-sensing pathways in cancer.
  • To understand the prognostic implications of these pathways in a pan-cancer cohort.
  • To explore the therapeutic potential of nucleic acid recognition in cancer treatment.

Main Methods:

  • Utilized multidimensional data from The Cancer Genome Atlas (TCGA) pan-cancer cohort.
  • Analyzed the expression of 15 key genes in the nucleic acid-sensing pathway.
  • Clustered cancer patients into subgroups based on gene expression for prognostic analysis.

Main Results:

  • Upregulation of cytosolic DNA-sensing genes (e.g., AIM2, cGAS) is common in tumor tissues.
  • Higher expression of nucleic acid-sensing pathway genes correlates with poorer prognosis across most cancer types.
  • In homologous recombination deficient (HRD) patients, activated nucleic acid recognition is associated with better prognosis, suggesting therapeutic efficacy.

Conclusions:

  • Dysregulation of nucleic acid-sensing pathways plays a significant role in cancer development and progression.
  • Prognostic and therapeutic implications of these pathways vary depending on cancer type and patient genetic background (e.g., HRD status).
  • This research provides a foundation for developing targeted nucleic acid-based cancer therapies and drugs.
Keywords:
cancer prognosisinnate immunitynucleic acid-sensingpancancer cohorttumor immunology

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