Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer

Autor: Gert Auer, Torbjörn Ramqvist, Jonas Kierkegaard, Masood Kamali-Moghaddam, Giuseppe Masucci, Bo Franzén, Thomas Hatschek, Andrey Alexeyenko, Lena Kanter, Ulf Landegren, Rolf Lewensohn
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Proteomics
Cancer Research
Cell- och molekylärbiologi
medicine.medical_treatment
Estrogen receptor
Cohort Studies
0302 clinical medicine
immune‐related protein biomarker
Breast
fine‐needle aspiration
Research Articles
medicine.diagnostic_test
General Medicine
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
Neoplasm Proteins
Fine-needle aspiration
Oncology
Receptors
Estrogen
030220 oncology & carcinogenesis
Molecular Medicine
CXCL9
Regression Analysis
Female
Chemokines
Research Article
immune-related protein biomarker
Biopsy
Fine-Needle
Breast Neoplasms
lcsh:RC254-282
GZMB
03 medical and health sciences
Breast cancer
Biopsy
Genetics
medicine
Humans
fine-needle aspiration
Cancer och onkologi
business.industry
Immunotherapy
medicine.disease
breast cancer subtypes
030104 developmental biology
Ki-67 Antigen
Cancer and Oncology
fibroadenomas
Cancer research
proximity extension assay
Cancer biomarkers
Neoplasm Grading
business
Cell and Molecular Biology
Zdroj: Molecular Oncology
Molecular Oncology, Vol 13, Iss 2, Pp 376-391 (2019)
ISSN: 1878-0261
1574-7891
Popis: There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and for follow‐up of personalized cancer therapy, including immunotherapy. Fine‐needle aspiration (FNA) biopsy provides ready access to relevant tissue samples; however, the minute amounts of sample require sensitive multiplex molecular analysis to be of clinical biomarker utility. We have applied proximity extension assays (PEA) to analyze 167 proteins in FNA samples from patients with breast cancer (BC; n = 25) and benign lesions (n = 32). We demonstrate that the FNA BC samples could be divided into two main clusters, characterized by differences in expression levels of the estrogen receptor (ER) and the proliferation marker Ki67. This clustering corresponded to some extent to established BC subtypes. Our analysis also revealed several proteins whose expression levels differed between BC and benign lesions (e.g., CA9, GZMB, IL‐6, VEGFA, CXCL11, PDL1, and PCD1), as well as several chemokines correlating with ER and Ki67 status (e.g., CCL4, CCL8, CCL20, CXCL8, CXCL9, and CXCL17). Finally, we also identified three signatures that could predict Ki67 status, ER status, and tumor grade, respectively, based on a small subset of proteins, which was dominated by chemokines. To our knowledge, expression profiles of CCL13 in benign lesions and BC have not previously been described but were shown herein to correlate with proliferation (P = 0.00095), suggesting a role in advanced BC. Given the broad functional range of the proteins analyzed, immune‐related proteins were overrepresented among the observed alterations. Our pilot study supports the emerging role of chemokines in BC progression. Due to the minimally traumatic sampling and clinically important molecular information for therapeutic decisions, this methodology is promising for future immunoscoring and monitoring of treatment efficacy in BC.
Databáze: OpenAIRE
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