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Series GSE253650 Query DataSets for GSE253650
Status Public on Apr 14, 2024
Title Biological Effects of Intraoperative Radiation Therapy (IORT): Histopathological Changes and Immunomodulation in Breast Cancer Patients
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary 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.
 
Overall design We selected a cohort of patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma who underwent breast-conserving surgery requiring margin re-excision. Histopathological evaluation and RNA-sequencing were performed from regions containing normal breast tissue, squamous metaplasia (SM), and squamous metaplasia with atypia (SMwA) in the re-excision specimens and compared between patients with IORT (n=11) vs. non-IORT (n=11).
 
Contributor(s) Orozco JI, Valdez BJ, Matsuba C, Ensenyat-Mendez M, Takasumi Y, Grumley JG
Citation(s) 38720889
Submission date Jan 18, 2024
Last update date Jul 17, 2024
Contact name Javier Orozco
E-mail(s) javier.orozco@providence.org
Organization name Saint John's Cancer Institute
Street address 2200 Santa Monica Blvd
City Santa Monica
State/province CA
ZIP/Postal code 90404
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (37)
GSM8024544 Pt_1_Normal_non-IORT
GSM8024545 Pt_2_Normal.region_1_non-IORT
GSM8024546 Pt_2_Normal.region_2_non-IORT
Relations
BioProject PRJNA1066480

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE253650_Merged.ReadsPerGene_NoNormalized.csv.gz 2.7 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA

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