Biological Effects of Intraoperative Radiation Therapy (IORT): Histopathological Changes and Immunomodulation in Breast Cancer Patients
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ABSTRACT:
PROVIDER: PRJNA1066480 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27638607_1.fastq.gz | Fastqsanger.gz | |||
| SRR27638607_2.fastq.gz | Fastqsanger.gz | |||
| SRR27638608_1.fastq.gz | Fastqsanger.gz | |||
| SRR27638608_2.fastq.gz | Fastqsanger.gz | |||
| SRR27638609_1.fastq.gz | Fastqsanger.gz |
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Project description:Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose directly to the breast tumor bed. The synergistic effects of simultaneous surgery and radiation are poorly understood. We here explored the cellular and molecular changes induced by IORT in the tumor bed compared to no-IORT exposed breast tissues. Squamous metaplasia (SM) was identified in both cohorts; however, squamous metaplasia with atypia (SMwA) was only seen in IORT specimens (63.6%, p=0.004). SMwA mimicked DCIS on histology, requiring confirmatory stains (i.e., estrogen receptor and p63) for diagnosis. Neither SM nor SMwA were found in the initial BCS specimen. We identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). Notably, when only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling (p<0.001). Finally, we inferred a higher abundance of gamma delta T-cells, dendritic cells, and monocytes in the IORT samples compared to non-IORT samples. In conclusion, IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with intrinsic apoptotic signaling and immune response pathways. The higher abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity in traditionally considered immune-desert tumors such as HR-positive/HER2-negative breast cancer.
2024-04-14 | GSE253650 | GEO
Project description:Intraoperative radiotherapy (IOERT) is a high radiation therapeutic technique which administers a single high dose of ionizing radiation (IR) immediately after surgical tumor removal in order to destroy the residual cancer cells in the site at high risk for recurrence. IR is able to regulate several genes and factors involved in cell-cycle progression, survival and/or cell death, DNA repair and inflammation modulating an intracellular response radiation dependent producing an imbalance in cell fate decision. In this study, we examined changes in gene expression in MCF7 breast cancer cell line exposed to 9Gy and 23Gy high single dose of IR delivered by IOERT.
2015-06-11 | GSE63667 | GEO
Project description:Intraoperative radiotherapy (IOERT) is a high radiation therapeutic technique which administers a single high dose of ionizing radiation (IR) immediately after surgical tumor removal in order to destroy the residual cancer cells in the site at high risk for recurrence. IR is able to regulate several genes and factors involved in cell-cycle progression, survival and/or cell death, DNA repair and inflammation modulating an intracellular response radiation dependent producing an imbalance in cell fate decision. In this study, we examined changes in gene expression in MCF7 breast cancer cell line exposed to 9Gy and 23Gy high single dose of IR delivered by IOERT. Changes in gene expression in MCF7 breast cancer cell line exposed to 9Gy and 23Gy high single dose of IR (named MCF7_9Gy and MCF7_23Gy respectively), were analyzed as two-color hybridizations using Agilent Technologies whole human genome 4x44K microarrays
2015-06-11 | E-GEOD-63667 | biostudies-arrayexpress
Project description:Transcriptomic profiling of breast cancer cells incubated in vitro with surgical wound fluids from patients with breast cancer reveals similarities in the biological response induced by intraoperative radiation therapy and the radiation-induced bystander effect In patients with breast cancer who undergo breast-conserving surgery (BCS), more than 90% of local recurrences occur in the same quadrant as the primary cancer. Surgical wound fluids (SWF) are believed to play a role in this process by inducing an inflammatory process in the scar tissue area. Despite strong clinical data demonstrating the benefits of intraoperative radiotherapy (IORT), the biological basis underlying this process remains poorly understood. Ionizing radiation (IR) directly affects cells by damaging DNA, thereby altering the cell phenotype. IR direct effects cancer cells and also influences unirradiated cells located nearby, a phenomenon known as the radiation-induced bystander effect (RIBE), significantly modifying the tumour microenvironment. We hypothesized that SWF obtained from patients after breast-conserving surgery (BCS) and IORT would induce a radiobiological response (due to RIBE) in unirradiated cells, thereby modifying their phenotype.
2019-08-01 | GSE135204 | GEO
Project description:Objective: Head and neck cancer (HNC) accounts for almost 850,000 new cases per year. Radiotherapy (RT) is used to treat the majority of these patients. A common side-effect of RT-treatment is onset of oral mucositis: a painful irritation and swelling in mouth, which decreases the quality of life and is the major dose-limiting factor in RT. To understand the origin of oral mucositis, the biological mechanisms post-ionizing radiation (IR) need to be understood. This knowledge can be used to develop new treatment targets for oral mucositis and markers for the early identification of “at risk” patients. Results: Mass spectrometry-based proteomics identified 5879 proteins in primary keratinocytes and 4597 proteins in OKF6 cells. Amongst them, 212 proteins in primary keratinocytes and 169 proteins in OKF6 cells were significantly differentially abundant 96 h after 6 Gy irradiation compared to sham-irradiated controls. Protein-protein in silico enrichment predicted interferon (IFN) response and DNA strand elongation pathways as mostly affected pathways in both cell systems. Both pathways were confirmed in OKF6 cells. Immunoblot validations showed a decrease in minichromosome maintenance (MCM) complex proteins 2-7 and an increase in IFN associated proteins STAT1 and ISG15. In line with affected IFN signalling, mRNA levels of IFNβ and interleukin 6 (IL-6) increased significantly following irradiation and also levels of secreted IL-1β IL-6, IP-10, and ISG15 were elevated. Conclusion: This study has investigated biological mechanisms in keratinocytes post-in vitro ionizing radiation. A common radiation signature in keratinocytes was identified. A role of IFN response in keratinocytes along with increased levels of pro-inflammatory cytokines and proteins could hint towards a possible mechanism for oral mucositis.
2023-06-09 | PXD040398 | Pride
Project description:Radiation therapy is a mainstay of cancer treatment, with more than 50% of all cancer patients receiving radiation during the course of their disease. Tumor irradiation can activate both innate and adaptive immune responses, and these responses can be pro- or anti-tumor growth . These observations have led to the search for antitumor approaches combining radiotherapy and specific immunotherapies, most commonly strategies promoting the systemic activation of T cells. Thus far, however, many cancer patients still suffer from local recurrence and/or untreatable metastatic disease after radiotherapy. Here we combine radiotherapy with activation of macrophage-mediated phagocytosis via blockade of the ?don?t-eat-me? cell surface molecule CD47 in small-cell lung cancer (SCLC), a highly metastatic form of lung cancer for which treatment options remain limited. We found that irradiation of SCLC cells in culture results in the secretion of inflammatory cytokines that results in increased migration and phagocytosis by macrophages. In vivo, CD47 blockade potently enhances the local antitumor effects of radiation therapy in murine and human pre-clinical models of SCLC. Strikingly, CD47 blockade also stimulates abscopal antitumor effects inhibiting the growth of non-irradiated SCLC tumors in mice receiving radiation. Similar abscopal antitumor effects were observed in colon cancer and lymphoma models. Surprisingly, these abscopal effects are completely independent of T cells but require macrophages that migrate into the non-irradiated tumor sites in response to inflammatory signals mediated by radiation and are locally activated by CD47 blockade to eliminate cancer cells. The systemic activation of antitumor macrophages following radiotherapy and CD47 blockade may be particularly important in cancer patients who suffer from metastatic disease.
2022-09-29 | GSE156106 | GEO
Project description:Introduction Cancer is the second leading cause of death in the United States, with breast cancer being the most commonly diagnosed new cancer in women. Radiation therapy provides well-documented survival and recurrence benefits; however, it can lead to significant adverse effects, such as radiation-induced fibrosis (RIF), which can cause pain and result in poor aesthetic outcomes. The biological mechanisms underlying RIF are not entirely understood and require further investigation to identify potential intervention avenues. In this study, we investigated the biological response to radiotherapy by analyzing non-irradiated and irradiated tissues from breast cancer patients. Materials and methods We collected tissue from breast cancer patients who underwent unilateral radiation and bilateral breast reconstruction. At the time of final reconstruction (post-radiation), samples were collected from both non-irradiated and irradiated reconstruction sites. These samples were analyzed using bulk RNA sequencing, histology, and immunohistochemistry (IHC). Results In fibrous tissue capsules, CLCA2, COL4A5, and COL6A6 were differentially expressed and may be related to reduced micro-vascularization. CXCL9 and PTCHD4 were upregulated within the skin, possibly conferring an increased immune response, while multiple keratin-related genes (KRT6B, KRT17, KRT25, KRT28, and KRT75) were downregulated. In irradiated muscle tissue, there was increased expression of CXCL10 and downregulation of DCD. These results were confirmed using IHC. Conclusions This study highlights the utility of bulk RNA sequencing studies in conjunction with IHC to identify target genes and biological processes responsible for RIF in tissues at final breast reconstruction. Due to the sample size limitation, further research is warranted to understand the role of keratin and collagen genes in regulating epidermal changes, vascularity, and fibrosis.
2024-09-27 | GSE278183 | GEO
Project description:Different DIPG tumor models have different responses to radiation therapy, which can be identified by quantitative proteomics/phospho-proteomics approach
2024-05-21 | PXD028285 | Pride
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