Back to Search
Start Over
Tumour radiosensitivity is associated with immune activation in solid tumours.
- Source :
-
European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2017 Oct; Vol. 84, pp. 304-314. Date of Electronic Publication: 2017 Aug 29. - Publication Year :
- 2017
-
Abstract
- Purpose: Our goal was to determine whether tumour radiosensitivity is associated with activation of the immune system across all tumour types as measured by two gene expression signatures (GESs).<br />Methods: We identified 10,240 genomically profiled distinct solid primary tumours with gene expression analysis available from an institutional de-identified database. Two separate GESs were included in the analysis, the radiosensitivity index (RSI) GES (a 10-gene GES as a measure of radiosensitivity) and the 12-chemokine (12-CK) signature (a 12-gene GES as a measure of immune activation). We tested whether the RSI and 12-CK were associated with each other across all tumour samples and, in an exploratory analysis, their prognostic significance in predicting distant metastasis-free survival (DMFS) among a well-characterised, independent cohort of 282 early-stage breast cancer cases treated with surgery and post-operative radiation alone without systemic therapy. The lower the RSI score, the higher the tumour radiosensitivity; whereas, the higher the 12-CK score the higher the immune activation.<br />Results: Using an RSI cut-point of ≤0.3745, RSI-low tumours (n = 4,291, 41.9%) had a significantly higher median 12-CK GES value (0.54 [-0.136, 1.095]) compared with RSI-high tumours (-0.17 [-0.82, 0.42]; p < 0.001) across all tumour samples, indicating that radiosensitivity is associated with immune activation. In an exploratory analysis of early-stage breast cancer cases, a multivariable model with patient age, RSI and 12-CK provided a strong composite model for DMFS (p = 0.02), with RSI (hazard ratio [HR] 0.63 [95% confidence interval 0.36, 1.09]) and 12-CK (HR 0.66 [0.41, 1.04]) each providing comparable contributions.<br />Conclusions: Tumour radiosensitivity is associated with immune activation as measured by the two GESs.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Biomarkers, Tumor genetics
Breast Neoplasms genetics
Breast Neoplasms immunology
Breast Neoplasms mortality
Chemokines genetics
Databases, Genetic
Disease-Free Survival
Gene Expression Profiling
Genetic Predisposition to Disease
Humans
Kaplan-Meier Estimate
Netherlands
Phenotype
Proportional Hazards Models
Radiation Tolerance genetics
Radiotherapy, Adjuvant
Risk Factors
Time Factors
Transcriptome
Treatment Outcome
Tumor Microenvironment
Biomarkers, Tumor immunology
Breast Neoplasms radiotherapy
Chemokines immunology
Radiation Tolerance immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0852
- Volume :
- 84
- Database :
- MEDLINE
- Journal :
- European journal of cancer (Oxford, England : 1990)
- Publication Type :
- Academic Journal
- Accession number :
- 28863385
- Full Text :
- https://doi.org/10.1016/j.ejca.2017.08.001