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An Immune Gene Expression Risk Score for Distant Metastases after Radiotherapy for Cervical Cancer.

Jelena Lukovic1,2, Melania Pintilie1, Kathy Han1,2,3

  • 1Princess Margaret Cancer Centre, Toronto, Canada.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 5, 2024
PubMed
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A new 55-gene immune risk score helps identify cervical cancer patients at high risk of distant metastases (DM). This score predicts outcomes and correlates with a less immunogenic tumor microenvironment, aiding treatment decisions.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Cervical cancer treatment faces challenges in identifying patients prone to distant metastases (DM) post-radiotherapy.
  • Accurate risk stratification is crucial for personalized treatment strategies in cervical cancer.

Purpose of the Study:

  • To develop and validate an immune-based gene expression risk score for predicting distant metastases (DM) in cervical cancer patients.
  • To identify patients with cervical cancer who are at increased risk of developing distant metastases after treatment.

Main Methods:

  • Whole-transcriptome RNA sequencing of tumor biopsies from 81 cervical cancer patients.
  • Derivation of a 55-gene risk score using Cox modeling and principal component analysis from 4,723 immune-related genes.
  • Validation of the risk score in independent cohorts from the Norwegian Radium Hospital (NRH) and The Cancer Genome Atlas (TCGA).

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Main Results:

  • The 55-gene risk score significantly predicted distant metastases (DM) and cause-specific survival (CSS) in initial and validation cohorts.
  • Higher risk scores correlated with reduced tumor-infiltrating immune cells (e.g., CD8 T cells, M1/M2 macrophages).
  • Elevated risk scores were associated with lower expression of key immune-related genes, including chemokines and immune checkpoint regulators.

Conclusions:

  • The developed immune metastatic risk score effectively identifies cervical cancer patients at high risk of DM.
  • Findings suggest that high tumor mutational burden and an "immune-cold" microenvironment contribute to distant metastatic recurrence.
  • Further validation of this immune risk score is warranted for clinical application in cervical cancer management.