کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5526213 1547048 2017 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Tumour radiosensitivity is associated with immune activation in solid tumours
ترجمه فارسی عنوان
حساسیت رادیویی تومور با فعال سازی ایمنی در تومورهای جامد همراه است
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی


• There are data that suggest an interplay between response to radiation therapy and immune activation.
• If a gene expression signature (GES) could improve the identification of this interplay it would likely be deemed a success.
• We compared two GES for tumour radiosensitivity index (RSI) and immune activation (12-CK).
• RSI and 12-CK GES are associated across all tumour types.
• The combined RSI and 12-CK GES phenotype has the potential to improve our prognostic ability.

PurposeOur 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).MethodsWe 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.ResultsUsing 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.ConclusionsTumour radiosensitivity is associated with immune activation as measured by the two GESs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cancer - Volume 84, October 2017, Pages 304–314