Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients.
Biomarkers, Tumor
/ genetics
Breast Neoplasms
/ pathology
Cohort Studies
Complement C3
/ genetics
Down-Regulation
/ genetics
Female
Gene Expression Regulation, Neoplastic
Genes
/ immunology
Humans
Immunity, Innate
/ genetics
Immunohistochemistry
Lymph Nodes
/ pathology
Lymphatic Metastasis
/ genetics
Prognosis
Transcriptome
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 03 2021
03 03 2021
Historique:
received:
01
09
2020
accepted:
18
02
2021
entrez:
4
3
2021
pubmed:
5
3
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Immune system plays a dual role in cancer by either targeting or supporting neoplastic cells at various stages of disease, including metastasis. Yet, the exact immune-related transcriptome profiles of primary tumours (PT) and lymph node metastases (LNM) and their evolution during luminal breast cancer (BCa) dissemination remain undiscovered. In order to identify the immune-related transcriptome changes that accompany lymphatic spread, we analysed PT-LNM pairs of luminal BCa using NanoString technology. Decrease in complement C3-one of the top-downregulated genes, in LNM was validated at the protein level using immunohistochemistry. Thirty-three of 360 analysed genes were downregulated (9%), whereas only 3 (0.8%) upregulated in LNM when compared to the corresponding PT. In LNM, reduced expression was observed in genes related to innate immunity, particularly to the complement system (C1QB, C1S, C1R, C4B, CFB, C3, SERPING1 and C3AR1). In validation cohort, complement C3 protein was less frequently expressed in LNM than in PT and it was associated with worse prognosis. To conclude, local expression of the complement system components declines during lymphatic spread of non-metastatic luminal BCa, whilst further reduction of tumoral complement C3 in LNM is indicative for poor survival. This points to context-dependent role of complement C3 in BCa dissemination.
Identifiants
pubmed: 33658651
doi: 10.1038/s41598-021-84568-0
pii: 10.1038/s41598-021-84568-0
pmc: PMC7930267
doi:
Substances chimiques
Biomarkers, Tumor
0
Complement C3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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