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Short-term effect of Boost versus Radical doses of Intraoperative electron Radiotherapy in breast cancer tumor bed using high-throughput approaches

ABSTRACT: Importance: Intra-operative electron Radiation Therapy as a partial-breast single high dose radiotherapy, leads to decrease the local recurrence through tumor bed modification. Objective: This study designed to investigate short-term effect of the dose- dependent and -independent molecular mechanisms and biological pathway of tumor bed modification induced by Intra-operative electron Radiation Methods: Six random selected breast cancer patients entered into our study and all patients by referee to their pathological report were treated by doses of 12Gy as a Boost dose and 21Gy as a Radical dose and the samples were categorized into three groups which included: Margin Before irradiation, Margin After immediately irradiation and Margin 24 hours After irradiation. Resluts: Using mRNA-sequencing, ~6 Giga base clean data (20 Million Reads, 150 base pair) per individual sample and totally 125.3 million reads of transcriptome sequence were generated from the patient samples. Discussion: Appropriate Intra-operative electron Radiation Therapy short-term effects of molecular mechanisms in tumor bed seems to be dose-independent.

ORGANISM(S): Homo sapiens

PROVIDER: GSE119204 | GEO | 2018/08/30

REPOSITORIES: GEO

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Project description:This is a genome-wide approach to identifying genes persistently induced in the mouse mammary gland by acute whole body low dose ionizing radiation (10cGy), 1 and 4 weeks after exposure. Gene expression that is modified under these parameters were compared between Tgfb1 wild type and heterozygote littermates in order to determine which genes induced or repressed by radiation were mediated via Tgfb1 status. Differential gene expression was analyzed in Tgfb1 heterozygote and wild type littermate 4th mammary glands, after whole body exposure to an acute dose of 10cGy ionizing radiation. Estrus cycle was normalized in all mice two days prior to irradiation by injection with an estrogen and progesterone mixture. It is widely believed that the carcinogenic action of ionizing radiation is due to targeted DNA damage and resulting mutations, but there is also substantial evidence that non-targeted radiation effects alter epithelial phenotype and the stromal microenvironment. Activation of transforming growth factor beta 1 (TGFbeta) is a non-targeted radiation effect that mediates cell fate decisions following DNA damage and regulates microenvironment composition; it could either suppress or promote cancer. Gene expression profiling shown herein demonstrates that low dose radiation (10 cGy) elicits persistent changes in Tgfb1 wild type and heterozygote murine mammary gland that are highly modulated by TGFbeta. We asked if such non-targeted radiation effects contribute to carcinogenesis by using a novel radiation chimera model. Unirradiated Trp53 null mammary epithelium was transplanted to the mammary stroma of mice previously exposed to a single low (10 -100 cGy) radiation dose. By 300 days, 100% of transplants in irradiated hosts at either 10 or 100 cGy had developed Trp53 null breast carcinomas compared to 54% in unirradiated hosts. Tumor growth rate was also increased by high, but not low, dose host irradiation. In contrast, irradiation of Tgfb1 heterozygote mice prior to transplantation failed to decrease tumor latency, or increase growth rate at any dose. Host irradiation significantly reduced the latency of invasive ductal carcinoma compared to spindle cell carcinoma, as well as those tumors negative for smooth muscle actin in wild type but not Tgfb1 heterozygote mice. However, irradiation of either host genotype significantly increased the frequency of estrogen receptor negative tumors. These data demonstrate two concepts critical to understanding radiation risks. First, non-targeted radiation effects can significantly promote the frequency and alter the features of epithelial cancer. Second, radiation-induced TGFbeta activity is a key mechanism of tumor promotion. Keywords: Differential gene expression after low dose irradiation Two genotypes: TGBbeta1 heterozygote and wildtype mouse mammary glands. Two time points post-10cGy-irradiation per genotype (1 week, 4 weeks); control time point was 1 week post-sham-irradiation. Two or three replicates per time point.

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Short-term effect of Boost versus Radical doses of Intraoperative electron Radiotherapy in breast cancer tumor bed using high-throughput approaches

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