Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression

Tumor-to-stroma ratio (TSR) is a prognostic factor that expresses the relative amounts of tumor and intratumoral stroma. In this study, its clinical and molecular relevance was evaluated in prostate cancer (PCa). The feasibility of automated quantification was tested in digital scans of tissue micro...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Paulina Nastały, Julia Smentoch, Marta Popęda, Emanuele Martini, Paolo Maiuri, Anna J. Żaczek, Marek Sowa, Marcin Matuszewski, Jolanta Szade, Leszek Kalinowski, Magdalena Niemira, Burkhard Brandt, Elke Eltze, Axel Semjonow, Natalia Bednarz-Knoll
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	prostate cancer tumor-to-stroma ratio biochemical recurrence tumor progression digital pathology Medicine R
Acceso en línea:	https://doaj.org/article/b971807204f74bcc94a74c1c91ae5695
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b971807204f74bcc94a74c1c91ae5695
record_format	dspace
spelling	oai:doaj.org-article:b971807204f74bcc94a74c1c91ae56952021-11-25T18:07:03ZLow Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression10.3390/jpm111110882075-4426https://doaj.org/article/b971807204f74bcc94a74c1c91ae56952021-10-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1088https://doaj.org/toc/2075-4426Tumor-to-stroma ratio (TSR) is a prognostic factor that expresses the relative amounts of tumor and intratumoral stroma. In this study, its clinical and molecular relevance was evaluated in prostate cancer (PCa). The feasibility of automated quantification was tested in digital scans of tissue microarrays containing 128 primary tumors from 72 PCa patients stained immunohistochemically for epithelial cell adhesion molecule (EpCAM), followed by validation in a cohort of 310 primary tumors from 209 PCa patients. In order to investigate the gene expression differences between tumors with low and high TSR, we applied multigene expression analysis (nCounter<sup>®</sup> PanCancer Progression Panel, NanoString) of 42 tissue samples. TSR scores were categorized into low (<1 TSR) and high (≥1 TSR). In the pilot cohort, 31 patients (43.1%) were categorized as low and 41 (56.9%) as high TSR score, whereas 48 (23.0%) patients from the validation cohort were classified as low TSR and 161 (77.0%) as high. In both cohorts, high TSR appeared to indicate the shorter time to biochemical recurrence in PCa patients (Log-rank test, <i>p</i> = 0.04 and <i>p</i> = 0.01 for the pilot and validation cohort, respectively). Additionally, in the multivariate analysis of the validation cohort, TSR predicted BR independent of other factors, i.e., pT, pN, and age (<i>p</i> = 0.04, HR 2.75, 95%CI 1.07–7.03). Our data revealed that tumors categorized into low and high TSR score show differential expression of various genes; the genes upregulated in tumors with low TSR score were mostly associated with extracellular matrix and cell adhesion regulation. Taken together, this study shows that high stroma content can play a protective role in PCa. Automatic EpCAM-based quantification of TSR might improve prognostication in personalized medicine for PCa.Paulina NastałyJulia SmentochMarta PopędaEmanuele MartiniPaolo MaiuriAnna J. ŻaczekMarek SowaMarcin MatuszewskiJolanta SzadeLeszek KalinowskiMagdalena NiemiraBurkhard BrandtElke EltzeAxel SemjonowNatalia Bednarz-KnollMDPI AGarticleprostate cancertumor-to-stroma ratiobiochemical recurrencetumor progressiondigital pathologyMedicineRENJournal of Personalized Medicine, Vol 11, Iss 1088, p 1088 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostate cancer tumor-to-stroma ratio biochemical recurrence tumor progression digital pathology Medicine R
spellingShingle	prostate cancer tumor-to-stroma ratio biochemical recurrence tumor progression digital pathology Medicine R Paulina Nastały Julia Smentoch Marta Popęda Emanuele Martini Paolo Maiuri Anna J. Żaczek Marek Sowa Marcin Matuszewski Jolanta Szade Leszek Kalinowski Magdalena Niemira Burkhard Brandt Elke Eltze Axel Semjonow Natalia Bednarz-Knoll Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression
description	Tumor-to-stroma ratio (TSR) is a prognostic factor that expresses the relative amounts of tumor and intratumoral stroma. In this study, its clinical and molecular relevance was evaluated in prostate cancer (PCa). The feasibility of automated quantification was tested in digital scans of tissue microarrays containing 128 primary tumors from 72 PCa patients stained immunohistochemically for epithelial cell adhesion molecule (EpCAM), followed by validation in a cohort of 310 primary tumors from 209 PCa patients. In order to investigate the gene expression differences between tumors with low and high TSR, we applied multigene expression analysis (nCounter<sup>®</sup> PanCancer Progression Panel, NanoString) of 42 tissue samples. TSR scores were categorized into low (<1 TSR) and high (≥1 TSR). In the pilot cohort, 31 patients (43.1%) were categorized as low and 41 (56.9%) as high TSR score, whereas 48 (23.0%) patients from the validation cohort were classified as low TSR and 161 (77.0%) as high. In both cohorts, high TSR appeared to indicate the shorter time to biochemical recurrence in PCa patients (Log-rank test, <i>p</i> = 0.04 and <i>p</i> = 0.01 for the pilot and validation cohort, respectively). Additionally, in the multivariate analysis of the validation cohort, TSR predicted BR independent of other factors, i.e., pT, pN, and age (<i>p</i> = 0.04, HR 2.75, 95%CI 1.07–7.03). Our data revealed that tumors categorized into low and high TSR score show differential expression of various genes; the genes upregulated in tumors with low TSR score were mostly associated with extracellular matrix and cell adhesion regulation. Taken together, this study shows that high stroma content can play a protective role in PCa. Automatic EpCAM-based quantification of TSR might improve prognostication in personalized medicine for PCa.
format	article
author	Paulina Nastały Julia Smentoch Marta Popęda Emanuele Martini Paolo Maiuri Anna J. Żaczek Marek Sowa Marcin Matuszewski Jolanta Szade Leszek Kalinowski Magdalena Niemira Burkhard Brandt Elke Eltze Axel Semjonow Natalia Bednarz-Knoll
author_facet	Paulina Nastały Julia Smentoch Marta Popęda Emanuele Martini Paolo Maiuri Anna J. Żaczek Marek Sowa Marcin Matuszewski Jolanta Szade Leszek Kalinowski Magdalena Niemira Burkhard Brandt Elke Eltze Axel Semjonow Natalia Bednarz-Knoll
author_sort	Paulina Nastały
title	Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression
title_short	Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression
title_full	Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression
title_fullStr	Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression
title_full_unstemmed	Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression
title_sort	low tumor-to-stroma ratio reflects protective role of stroma against prostate cancer progression
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b971807204f74bcc94a74c1c91ae5695
work_keys_str_mv	AT paulinanastały lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT juliasmentoch lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT martapopeda lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT emanuelemartini lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT paolomaiuri lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT annajzaczek lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT mareksowa lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT marcinmatuszewski lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT jolantaszade lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT leszekkalinowski lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT magdalenaniemira lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT burkhardbrandt lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT elkeeltze lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT axelsemjonow lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression AT nataliabednarzknoll lowtumortostromaratioreflectsprotectiveroleofstromaagainstprostatecancerprogression
_version_	1718411639093460992

Low Tumor-to-Stroma Ratio Reflects Protective Role of Stroma against Prostate Cancer Progression

Ejemplares similares