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Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer
SIMPLE SUMMARY: The coexistence of genetically distinct cancer cell clones, their phenotypic plasticity, and the presence of different constituents of the tumor microenvironment create intra-tumor heterogeneity, which affects cancer development and its response to therapy. We observed that a higher...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431441/ https://www.ncbi.nlm.nih.gov/pubmed/34503159 http://dx.doi.org/10.3390/cancers13174349 |
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author | Gawin, Marta Kurczyk, Agata Niemiec, Joanna Stanek-Widera, Agata Grela-Wojewoda, Aleksandra Adamczyk, Agnieszka Biskup-Frużyńska, Magdalena Polańska, Joanna Widłak, Piotr |
author_facet | Gawin, Marta Kurczyk, Agata Niemiec, Joanna Stanek-Widera, Agata Grela-Wojewoda, Aleksandra Adamczyk, Agnieszka Biskup-Frużyńska, Magdalena Polańska, Joanna Widłak, Piotr |
author_sort | Gawin, Marta |
collection | PubMed |
description | SIMPLE SUMMARY: The coexistence of genetically distinct cancer cell clones, their phenotypic plasticity, and the presence of different constituents of the tumor microenvironment create intra-tumor heterogeneity, which affects cancer development and its response to therapy. We observed that a higher degree of phenotypic heterogeneity revealed by mass spectrometry imaging was associated with a favorable outcome in HER2-positive breast cancer. This phenomenon putatively reflects the presence of heterotypic components of the microenvironment, which could facilitate the response to anticancer treatment. ABSTRACT: Intra-tumor heterogeneity (ITH) results from the coexistence of genetically distinct cancer cell (sub)populations, their phenotypic plasticity, and the presence of heterotypic components of the tumor microenvironment (TME). Here we addressed the potential association between phenotypic ITH revealed by mass spectrometry imaging (MSI) and the prognosis of breast cancer. Tissue specimens resected from 59 patients treated radically due to the locally advanced HER2-positive invasive ductal carcinoma were included in the study. After the on-tissue trypsin digestion of cellular proteins, peptide maps of all cancer regions (about 380,000 spectra in total) were segmented by an unsupervised approach to reveal their intrinsic heterogeneity. A high degree of similarity between spectra was observed, which indicated the relative homogeneity of cancer regions. However, when the number and diversity of the detected clusters of spectra were analyzed, differences between patient groups were observed. It is noteworthy that a higher degree of heterogeneity was found in tumors from patients who remained disease-free during a 5-year follow-up (n = 38) compared to tumors from patients with progressive disease (distant metastases detected during the follow-up, n = 21). Interestingly, such differences were not observed between patients with a different status of regional lymph nodes, cancer grade, or expression of estrogen receptor at the time of the primary treatment. Subsequently, spectral components with different abundance in cancer regions were detected in patients with different outcomes, and their hypothetical identity was established by assignment to measured masses of tryptic peptides identified in corresponding tissue lysates. Such differentiating components were associated with proteins involved in immune regulation and hemostasis. Further, a positive correlation between the level of tumor-infiltrating lymphocytes and heterogeneity revealed by MSI was observed. We postulate that a higher heterogeneity of tumors with a better prognosis could reflect the presence of heterotypic components including infiltrating immune cells, that facilitated the response to treatment. |
format | Online Article Text |
id | pubmed-8431441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84314412021-09-11 Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer Gawin, Marta Kurczyk, Agata Niemiec, Joanna Stanek-Widera, Agata Grela-Wojewoda, Aleksandra Adamczyk, Agnieszka Biskup-Frużyńska, Magdalena Polańska, Joanna Widłak, Piotr Cancers (Basel) Communication SIMPLE SUMMARY: The coexistence of genetically distinct cancer cell clones, their phenotypic plasticity, and the presence of different constituents of the tumor microenvironment create intra-tumor heterogeneity, which affects cancer development and its response to therapy. We observed that a higher degree of phenotypic heterogeneity revealed by mass spectrometry imaging was associated with a favorable outcome in HER2-positive breast cancer. This phenomenon putatively reflects the presence of heterotypic components of the microenvironment, which could facilitate the response to anticancer treatment. ABSTRACT: Intra-tumor heterogeneity (ITH) results from the coexistence of genetically distinct cancer cell (sub)populations, their phenotypic plasticity, and the presence of heterotypic components of the tumor microenvironment (TME). Here we addressed the potential association between phenotypic ITH revealed by mass spectrometry imaging (MSI) and the prognosis of breast cancer. Tissue specimens resected from 59 patients treated radically due to the locally advanced HER2-positive invasive ductal carcinoma were included in the study. After the on-tissue trypsin digestion of cellular proteins, peptide maps of all cancer regions (about 380,000 spectra in total) were segmented by an unsupervised approach to reveal their intrinsic heterogeneity. A high degree of similarity between spectra was observed, which indicated the relative homogeneity of cancer regions. However, when the number and diversity of the detected clusters of spectra were analyzed, differences between patient groups were observed. It is noteworthy that a higher degree of heterogeneity was found in tumors from patients who remained disease-free during a 5-year follow-up (n = 38) compared to tumors from patients with progressive disease (distant metastases detected during the follow-up, n = 21). Interestingly, such differences were not observed between patients with a different status of regional lymph nodes, cancer grade, or expression of estrogen receptor at the time of the primary treatment. Subsequently, spectral components with different abundance in cancer regions were detected in patients with different outcomes, and their hypothetical identity was established by assignment to measured masses of tryptic peptides identified in corresponding tissue lysates. Such differentiating components were associated with proteins involved in immune regulation and hemostasis. Further, a positive correlation between the level of tumor-infiltrating lymphocytes and heterogeneity revealed by MSI was observed. We postulate that a higher heterogeneity of tumors with a better prognosis could reflect the presence of heterotypic components including infiltrating immune cells, that facilitated the response to treatment. MDPI 2021-08-27 /pmc/articles/PMC8431441/ /pubmed/34503159 http://dx.doi.org/10.3390/cancers13174349 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Gawin, Marta Kurczyk, Agata Niemiec, Joanna Stanek-Widera, Agata Grela-Wojewoda, Aleksandra Adamczyk, Agnieszka Biskup-Frużyńska, Magdalena Polańska, Joanna Widłak, Piotr Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer |
title | Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer |
title_full | Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer |
title_fullStr | Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer |
title_full_unstemmed | Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer |
title_short | Intra-Tumor Heterogeneity Revealed by Mass Spectrometry Imaging Is Associated with the Prognosis of Breast Cancer |
title_sort | intra-tumor heterogeneity revealed by mass spectrometry imaging is associated with the prognosis of breast cancer |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431441/ https://www.ncbi.nlm.nih.gov/pubmed/34503159 http://dx.doi.org/10.3390/cancers13174349 |
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