Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Differences in the Tumor Molecular and Microenvironmental Land-Scape Between Early (Non-metastatic) and De Novo Metastatic Primary Luminal Breast Tumors

Yentl Lambrechts
ORCID logo ,
Sigrid Hatse
* ORCID logo ,
François Richard
ORCID logo ,
Bram Boeckx
,
Giuseppe Floris
,
Christine Desmedt
,
Ann Smeets
,
Patrick Neven
ORCID logo ,
Diether Lambrechts
,
Hans Wildiers
ORCID logo
Version 1 : Received: 26 June 2023 / Approved: 27 June 2023 / Online: 27 June 2023 (04:47:03 CEST)

A peer-reviewed article of this Preprint also exists.

Lambrechts, Y.; Hatse, S.; Richard, F.; Boeckx, B.; Floris, G.; Desmedt, C.; Smeets, A.; Neven, P.; Lambrechts, D.; Wildiers, H. Differences in the Tumor Molecular and Microenvironmental Landscape between Early (Non-Metastatic) and De Novo Metastatic Primary Luminal Breast Tumors. Cancers 2023, 15, 4341. Lambrechts, Y.; Hatse, S.; Richard, F.; Boeckx, B.; Floris, G.; Desmedt, C.; Smeets, A.; Neven, P.; Lambrechts, D.; Wildiers, H. Differences in the Tumor Molecular and Microenvironmental Landscape between Early (Non-Metastatic) and De Novo Metastatic Primary Luminal Breast Tumors. Cancers 2023, 15, 4341.

Abstract

Background. The molecular mechanisms underlying de novo metastasis of luminal breast cancer (dnMBC) remain largely unknown. Materials & Methods. Newly diagnosed dnMBC patients (grade 2/3, ER+, PR+/-, HER2-), with available core needle biopsy (CNB), collected from the primary tumor, were selected from our clinical-pathological database. Tumors from dnMBC patients were 1:1 pairwise matched (n=32) to tumors from newly diagnosed patients who had no distant metastases at baseline (eBC group). RNA was extracted from 5 x 10µm sections of FFPE CNBs. RNA sequencing was performed using the Illumina platform. Differentially expressed genes (DEG)s were assessed using EdgeR, deconvolution was performed using CIBERSORTx to assess immune cell fractions. Paired Wilcoxon test was used to compare dnMBC and eBC groups, and corrected for false discovery rate (FDR). Results. Many regulatory DEGs were significantly downregulated in dnMBC compared to eBC. Also, immune-related and hypoxia-related signatures were significantly upregulated. Paired Wilcoxon analysis showed that CCL17 and neutrophils fraction were significantly upregulated, whereas the memory B-cell fraction was significantly downregulated in the dnMBC group. Conclusion. Primary luminal tumors of dnMBC patients display significant transcriptomic and immunological differences compared to comparable tumors from eBC patients.

Keywords

(luminal) breast cancer; breast cancer biology; mutations; primary tumor; de novo - stage IV; tumor microenvironment

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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