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Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging

Different aspects of intra-tumor heterogeneity (ITH), which are associated with the development of cancer and its response to treatment, have postulated prognostic value. Here we searched for potential association between phenotypic ITH analyzed by mass spectrometry imaging (MSI) and prognosis of he...

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Autores principales: Kurczyk, Agata, Gawin, Marta, Paul, Piotr, Chmielik, Ewa, Rutkowski, Tomasz, Pietrowska, Monika, Widłak, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458238/
https://www.ncbi.nlm.nih.gov/pubmed/36080226
http://dx.doi.org/10.3390/molecules27175458
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author Kurczyk, Agata
Gawin, Marta
Paul, Piotr
Chmielik, Ewa
Rutkowski, Tomasz
Pietrowska, Monika
Widłak, Piotr
author_facet Kurczyk, Agata
Gawin, Marta
Paul, Piotr
Chmielik, Ewa
Rutkowski, Tomasz
Pietrowska, Monika
Widłak, Piotr
author_sort Kurczyk, Agata
collection PubMed
description Different aspects of intra-tumor heterogeneity (ITH), which are associated with the development of cancer and its response to treatment, have postulated prognostic value. Here we searched for potential association between phenotypic ITH analyzed by mass spectrometry imaging (MSI) and prognosis of head and neck cancer. The study involved tissue specimens resected from 77 patients with locally advanced oral squamous cell carcinoma, including 37 patients where matched samples of primary tumor and synchronous lymph node metastases were analyzed. A 3-year follow-up was available for all patients which enabled their separation into two groups: with no evidence of disease (NED, n = 41) and with progressive disease (PD, n = 36). After on-tissue trypsin digestion, peptide maps of all cancer regions were segmented using an unsupervised approach to reveal their intrinsic heterogeneity. We found that intra-tumor similarity of spectra was higher in the PD group and diversity of clusters identified during image segmentation was higher in the NED group, which indicated a higher level of ITH in patients with more favorable outcomes. Signature of molecular components that correlated with long-term outcomes could be associated with proteins involved in the immune functions. Furthermore, a positive correlation between ITH and histopathological lymphocytic host response was observed. Hence, we proposed that a higher level of ITH revealed by MSI in cancers with a better prognosis could reflect the presence of heterotypic components of tumor microenvironment such as infiltrating immune cells enhancing the response to the treatment.
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spelling pubmed-94582382022-09-09 Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging Kurczyk, Agata Gawin, Marta Paul, Piotr Chmielik, Ewa Rutkowski, Tomasz Pietrowska, Monika Widłak, Piotr Molecules Article Different aspects of intra-tumor heterogeneity (ITH), which are associated with the development of cancer and its response to treatment, have postulated prognostic value. Here we searched for potential association between phenotypic ITH analyzed by mass spectrometry imaging (MSI) and prognosis of head and neck cancer. The study involved tissue specimens resected from 77 patients with locally advanced oral squamous cell carcinoma, including 37 patients where matched samples of primary tumor and synchronous lymph node metastases were analyzed. A 3-year follow-up was available for all patients which enabled their separation into two groups: with no evidence of disease (NED, n = 41) and with progressive disease (PD, n = 36). After on-tissue trypsin digestion, peptide maps of all cancer regions were segmented using an unsupervised approach to reveal their intrinsic heterogeneity. We found that intra-tumor similarity of spectra was higher in the PD group and diversity of clusters identified during image segmentation was higher in the NED group, which indicated a higher level of ITH in patients with more favorable outcomes. Signature of molecular components that correlated with long-term outcomes could be associated with proteins involved in the immune functions. Furthermore, a positive correlation between ITH and histopathological lymphocytic host response was observed. Hence, we proposed that a higher level of ITH revealed by MSI in cancers with a better prognosis could reflect the presence of heterotypic components of tumor microenvironment such as infiltrating immune cells enhancing the response to the treatment. MDPI 2022-08-25 /pmc/articles/PMC9458238/ /pubmed/36080226 http://dx.doi.org/10.3390/molecules27175458 Text en © 2022 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 Article
Kurczyk, Agata
Gawin, Marta
Paul, Piotr
Chmielik, Ewa
Rutkowski, Tomasz
Pietrowska, Monika
Widłak, Piotr
Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging
title Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging
title_full Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging
title_fullStr Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging
title_full_unstemmed Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging
title_short Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging
title_sort prognostic value of molecular intratumor heterogeneity in primary oral cancer and its lymph node metastases assessed by mass spectrometry imaging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458238/
https://www.ncbi.nlm.nih.gov/pubmed/36080226
http://dx.doi.org/10.3390/molecules27175458
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