Breast Cancer Plasticity after Chemotherapy Highlights the Need for Re-Evaluation of Subtyping in Residual Cancer and Metastatic Tissues


Demirkol Canlı S.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol.25, no.11, pp.6054-6065, 2024 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 25 Issue: 11
  • Publication Date: 2024
  • Doi Number: 10.3390/ijms25116054
  • Journal Name: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database, Directory of Open Access Journals
  • Page Numbers: pp.6054-6065
  • Hacettepe University Affiliated: Yes

Abstract

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Breast Cancer Plasticity after Chemotherapy Highlights the Need for Re-Evaluation of Subtyping in Residual Cancer and Metastatic Tissues

by 
Irena Barbara Padzińska-Pruszyńska
 1,
Muhammad Waqas Akbar
 2,
Murat Isbilen
 3,
Emilia Górka
 1,
Baris Kucukkaraduman
 2,
Seçil Demirkol Canlı
 4,
Ege Dedeoğlu
 2,
Shila Azizolli
 2,
Isli Cela
 2,
Abbas Guven Akcay
 2,
Hasim Hakanoglu
 2,5,
Lubomir Bodnar
 6,7,
Szczepan Cierniak
 8,
Zygmunt Kozielec
 9,10,
Jacek Jerzy Pruszyński
 11,
Martyna Bittel
 1,
Ali Osmay Gure
 12,
Magdalena Król
 1 and
Bartłomiej Taciak
 1,*
1
Center of Cellular Immunotherapies, Warsaw University of Life Sciences, 02-786 Warsaw, Poland
2
Department of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey
3
Department of Biostatistics and Bioinformatics, Acibadem University, Istanbul 34752, Turkey
4
Molecular Pathology Application and Research Center, Hacettepe University, Ankara 06100, Turkey
5
Department of Genetics and Bioengineering, Istanbul Bilgi University, Istanbul 34060, Turkey
6
Department of Clinical Oncology and Radiotherapy, St. John Paul II Mazovia Regional Hospital in Siedlce, 08-110 Siedlce, Poland
7
Faculty of Medical and Health Sciences, University of Natural Sciences and Humanities, 08-110 Siedlce, Poland
8
Department of Pathomorphology, Military Institute of Medicine, 04-141 Warsaw, Poland
9
Department of Pathomorphology, Warmian-Masurian Cancer Center of the Ministry of the Interior and Administration’s Hospital, 11-041 Olsztyn, Poland
10
Department of Pathomorphology, University of Warmia and Mazury, 10-719 Olsztyn, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 202425(11), 6054; https://doi.org/10.3390/ijms25116054
Submission received: 21 April 2024 / Revised: 7 May 2024 / Accepted: 19 May 2024 / Published: 31 May 2024
(This article belongs to the Special Issue Expression of Signaling Genes in Cancer and Other Pathologies)

Abstract

This research paper presents a novel approach to identifying biomarkers that can be used to prognosticate patients with triple-negative breast cancer (TNBC) eligible for neoadjuvant therapy. The study utilized survival and RNA sequencing data from a cohort of TNBC patients and identified 276 genes whose expression was related to survival in such patients. The gene expression data were then used to classify patients into two major groups based on the presence or absence of Wingless/Integrated-pathway (Wnt-pathway) and mesenchymal (Mes) markers (Wnt/Mes). Patients with a low expression of Wnt/Mes-related genes had a favorable outcome, with no deaths observed during follow-up, while patients with a high expression of Wnt/Mes genes had a higher mortality rate of 50% within 19 months. The identified gene list could be validated and potentially used to shape treatment options for TNBC patients eligible for neoadjuvant therapy providing valuable insights into the development of more effective treatments for TNBC. Our data also showed significant variation in gene expression profiles before and after chemotherapy, with most tumors switching to a more mesenchymal/stem cell-like profile. To verify this observation, we performed an in silico analysis to classify breast cancer tumors in Prediction Analysis of Microarray 50 (PAM50) molecular classes before treatment and after treatment using gene expression data. Our findings demonstrate that following drug intervention and metastasis, certain tumors undergo a transition to alternative subtypes, resulting in diminished therapeutic efficacy. This underscores the necessity for reevaluation of patients who have experienced relapse or metastasis post-chemotherapy, with a focus on molecular subtyping. Tailoring treatment strategies based on these refined subtypes is imperative to optimize therapeutic outcomes for affected individuals.