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Microenvironment-related genes expression profile from lymph nodes of breast cancer patients using OSNA samples

ABSTRACT: The One Step Nucleic Acid Amplification (OSNA) assay is used to identify occult metastases in the axillary Sentinel Lymph Nodes (SLNs) of early stage breast cancer patients by quantification of the expression of cytokeratin19 (CK19) gene. The discarded samples of OSNA assay were explored as a source of information of SLN microenvironment response in patients with early stage Luminal A breast cancer using an RNAseq panel. Funding: project “GenomePT—National Laboratory for Genome Sequencing and Analysis” (POCI-01-0145-FEDER-022184), and project “Central Region Training Project for Personalized/Precision Medicine, with a genomic basis”, financed by the program CENTRO2020 [CENTRO-08-5864-FSE-000039 (PEP IN1194) 07-2021].

ORGANISM(S): Homo sapiens

PROVIDER: GSE210006 | GEO | 2023/01/06

REPOSITORIES: GEO

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Project description:Normal-appearing epithelium of cancer patients can harbor occult genetic abnormalities. Data comprehensively comparing gene expression between histologically normal breast epithelium of breast cancer patients and cancer-free controls are limited. The present study compares global gene expression between these groups. We performed microarrays using RNA from microdissected histologically normal terminal ductal-lobular units (TDLU) from 2 groups: (i) cancer normal (CN) (TDLUs adjacent to untreated ER1 breast cancers (n = 14)) and (ii) reduction mammoplasty (RM) (TDLUs of age-matched women without breast disease (n = 15)). Cyber-T identi?ed differentially expressed genes. Quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC), and comparison to independent microarray data including 6 carcinomas in situ (CIS), validated the results. Gene ontology (GO), UniProt and published literature evaluated gene function. About 127 probesets, corresponding to 105 genes, were differentially expressed between CN and RM (p < 0.0009, corresponding to FDR <0.10). 104/127 (82%) probesets were also differentially expressed between CIS and RM, nearly always (102/104 (98%)) in the same direction as in CN vs. RM. Two-thirds of the 105 genes were implicated previously in carcinogenesis. Overrepresented functional groups included transcription, G-protein coupled and chemokine receptor activity, the MAPK cascade and immediate early genes. Most genes in these categories were under-expressed in CN vs. RM. We conclude that global gene expression abnormalities exist in normal epithelium of breast cancer patients and are also present in early cancers. Thus, cancer-related pathways may be perturbed in normal epithelium. These abnormalities could be markers of disease risk, occult disease, or the tissueâs response to an existing tumor. Experiment Overall Design: 29 samples from histologically normal microdissected breast epithelium are included in this series. 14 samples are from epithelium adjacent to a breast tumor, 15 samples were obtained from patients undergoing reduction mammoplasty without apparent breast cancer

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Microenvironment-related genes expression profile from lymph nodes of breast cancer patients using OSNA samples

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